ORCID Profile
0000-0003-1905-3586
Current Organisations
Singapore Immunology Network
,
University of New South Wales
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Publications
Neutrophils contribute to inflammatory lymphangiogenesis by increasing VEGF-A bioavailability and secreting VEGF-D.
Publisher: American Society of Hematology
Date: 21-11-2013
DOI: 10.1182/BLOOD-2012-11-466532
Abstract: Lymphangiogenesis is an important physiological response to inflammatory insult, acting to limit inflammation. Macrophages, dendritic cells, and lymphocytes are known to drive lymphangiogenesis. In this study, we show that neutrophils recruited to sites of inflammation can also coordinate lymphangiogenesis. In the absence of B cells, intranodal lymphangiogenesis induced during prolonged inflammation as a consequence of immunization is dependent on the accumulation of neutrophils. When neutrophils are depleted in wild-type mice developing skin inflammation in response to immunization or contact hypersensitization, lymphangiogenesis is decreased and local inflammation is increased. We demonstrate that neutrophils contribute to lymphangiogenesis primarily by modulating vascular endothelial growth factor (VEGF)-A bioavailability and bioactivity and, to a lesser extent, secreting VEGF-D. We further show that neutrophils increased VEGF-A bioavailability and bioactivity via the secretion of matrix metalloproteinases 9 and heparanase. Together, these findings uncover a novel function for neutrophils as organizers of lymphangiogenesis during inflammation.
Granulopoiesis and Neutrophil Homeostasis: A Metabolic, Daily Balancing Act
Publisher: No publisher found
Understanding the Murine Cutaneous Dendritic Cell Network to Improve Intradermal Vaccination Strategies
Publisher: No publisher found
Two distinct interstitial macrophage populations coexist across tissues in specific subtissular niches
Publisher: No publisher found
Lung endothelial cell antigen cross-presentation to CD8+T cells drives malaria-associated lung injury
Publisher: Springer Science and Business Media LLC
Date: 18-09-2019
DOI: 10.1038/S41467-019-12017-8
Abstract: Malaria-associated acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) are life-threatening manifestations of severe malaria infections. The pathogenic mechanisms that lead to respiratory complications, such as vascular leakage, remain unclear. Here, we confirm that depleting CD8 + T cells with anti-CD8β antibodies in C57BL/6 mice infected with P. berghei ANKA (PbA) prevent pulmonary vascular leakage. When we transfer activated parasite-specific CD8 + T cells into PbA-infected TCRβ −/− mice (devoid of all T-cell populations), pulmonary vascular leakage recapitulates. Additionally, we demonstrate that PbA-infected erythrocyte accumulation leads to lung endothelial cell cross-presentation of parasite antigen to CD8 + T cells in an IFNγ−dependent manner. In conclusion, pulmonary vascular damage in ALI is a consequence of IFNγ-activated lung endothelial cells capturing, processing, and cross-presenting malaria parasite antigen to specific CD8 + T cells induced during infection. The mechanistic understanding of the immunopathogenesis in malaria-associated ARDS and ALI provide the basis for development of adjunct treatments.
Lights, camera, and action: vertebrate skin sets the stage for immune cell interaction with arthropod-vectored pathogens
Publisher: No publisher found
The BAFF/APRIL system: life beyond B lymphocytes
Publisher: No publisher found
Silica shelled and block copolymer encapsulated red-emissive AIE nanoparticles with 50% quantum yield for two-photon excited vascular imaging
Publisher: Royal Society of Chemistry (RSC)
Date: 2015
DOI: 10.1039/C5CC03603H
Abstract: A polymer and silica co-protection strategy has been developed to encapsulate organic fluorogens with aggregation-induced emission and charge transfer characteristics into small nanoparticles (NPs).
Random migration precedes stable target cell interactions of tumor-infiltrating T cells
Publisher: No publisher found
Organic nanoparticles with ultrahigh quantum yield and aggregation-induced emission characteristics for cellular imaging and real-time two-photon lung vasculature imaging
Publisher: No publisher found
DOI: 10.1039/C8TB00386F}
Glycopeptide antibiotic analogs for selective inactivation and two-photon imaging of vancomycin-resistant strains
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C5CC10230H
Abstract: Theranostic alent vancomycin systems exhibit selective antibacterial activity against vancomycin-resistant strains and can be applied for two-photon fluorescence imaging.
Ultrabright Organic Dots with Aggregation-Induced Emission Characteristics for Real-Time Two-Photon Intravital Vasculature Imaging
Publisher: No publisher found
Nanostring Analysis of Skin Biopsies from Patients with Henoch-Schönlein Purpura Reveals Genes Associated with Pathology and Heterogeneity in the Disease Process
Publisher: Medical Journals Sweden AB
Date: 2018
Perivascular macrophages mediate neutrophil recruitment during bacterial skin infection
Publisher: No publisher found
DOI: 10.1038/NI.2769}
Plasmodium vivax: restricted tropism and rapid remodeling of CD71-positive reticulocytes
Publisher: No publisher found
BAFF costimulation of Toll-like receptor-activated B-1 cells
Publisher: No publisher found
Development of nephritis but not sialadenitis in autoimmune-prone BAFF transgenic mice lacking marginal zone cells
Publisher: Wiley
Date: 09-2006
Abstract: B cell-activating factor belonging to the TNF family (BAFF) is a B cell survival factor required for B cell maturation. BAFF transgenic (Tg) mice develop autoimmune disorders characterized by autoantibody production, which leads to nephritis and salivary gland destruction (sialadenitis), features reminiscent of systemic lupus erythematosus and Sjögren's syndrome (SS), respectively. Disease in BAFF Tg mice correlates with the expansion of the marginal zone (MZ) B cell compartment and the abnormal presence of MZ-like B cells in the blood, LN and inflamed salivary glands, suggesting a role for these cells in BAFF-induced autoimmunity. Lymphotoxin-beta (LTbeta)-deficient mice show disrupted splenic architecture, lack MZ B cells and some peripheral LN, and are unable to mount T cell-dependent immune responses. BAFF Tg mice lacking LTbeta (LTbetaDelta-BTg) retained these defects, yet still developed nephritis associated with the presence of B-1 B cells in the kidneys. However, in contrast to old BAFF Tg mice, aging LTbetaDelta-BTg mice no longer developed sialadenitis. Thus, autoimmune disorders in BAFF Tg mice are possibly events coordinated by MZ and B-1 B cells at separate anatomical sites.
Visualization of bone marrow monocyte mobilization using Cx3cr1gfp/+Flt3L-/- reporter mouse by multiphoton intravital microscopy.
Publisher: Oxford University Press (OUP)
Date: 16-12-2015
Abstract: Monocytes are innate immune cells that play critical roles in inflammation and immune defense. A better comprehension of how monocytes are mobilized and recruited is fundamental to understand their biologic role in disease and steady state. The BM represents a major “checkpoint” for monocyte homeostasis, as it is the primary site for their production and release. Our study determined that the Cx3cr1gfp/+ mouse strain is currently the most ideal model for the visualization of monocyte behavior in the BM by multiphoton intravital microscopy. However, we observed that DCs are also labeled with high levels of GFP and thus, interfere with the accuracy of monocyte tracking in vivo. Hence, we generated a Cx3cr1gfp/+Flt3L−/− reporter mouse and showed that whereas monocyte numbers were not affected, DC numbers were reduced significantly, as DCs but not monocytes depend on Flt3 signaling for their development. We thus verified that mobilization of monocytes from the BM in Cx3cr1gfp/+Flt3L−/− mice is intact in response to LPS. Collectively, our study demonstrates that the Cx3cr1gfp/+Flt3L−/− reporter mouse model represents a powerful tool to visualize monocyte activities in BM and illustrates the potential of a Cx3cr1gfp/+-based, multifunctionality fluorescence reporter approach to dissect monocyte function in vivo.
A Three-Dimensional Atlas of Human Dermal Leukocytes, Lymphatics, and Blood Vessels
Publisher: No publisher found
Deciphering spatial domains from spatial multi-omics with SpatialGlue
Publisher: Research Square Platform LLC
Date: 16-05-2023
DOI: 10.21203/RS.3.RS-2921471/V1
Abstract: Integration of multiple data modalities in a spatially informed manner remains an unmet need for exploiting spatial multi-omics data. Here, we introduce SpatialGlue, a novel graph neural network with dual-attention mechanism, to decipher spatial domains by capturing the significance of each modality and neighbor graph in cross-omics and intra-omics integration. We demonstrate that SpatialGlue can accurately aggregate cell types into spatial domains at a higher resolution across different tissue types and technology platforms, as well as gain biological insights into cross-modality spatial correlations.
Anti-Allergic Inflammatory Activity of Interleukin-37 Is Mediated by Novel Signaling Cascades in Human Eosinophils
Publisher: No publisher found
MAP3K2-regulated intestinal stromal cells define a distinct stem cell niche
Publisher: Springer Science and Business Media LLC
Date: 03-03-2021
DOI: 10.1038/S41586-021-03283-Y
Abstract: Intestinal stromal cells are known to modulate the propagation and differentiation of intestinal stem cells
Targeted induction of antigen expression within dendritic cells modulates antigen-specific immunity afforded by recombinant BCG
Publisher: No publisher found
CXCR4 identifies transitional bone marrow premonocytes that replenish the mature monocyte pool for peripheral responses
Publisher: No publisher found
Two-photon imaging of effector T-cell behavior: lessons from a tumor model
Publisher: No publisher found
Silica shelled and block copolymer encapsulated red-emissive AIE nanoparticles with 50% quantum yield for two-photon excited vascular imaging
Publisher: No publisher found
DOI: 10.1039/C5CC03603H}
Cellular and transcriptional dynamics of human neutrophils at steady state and upon stress
Publisher: Springer Science and Business Media LLC
Date: 22-09-2022
DOI: 10.1038/S41590-022-01311-1
Abstract: Traditionally viewed as poorly plastic, neutrophils are now recognized as functionally erse however, the extent and determinants of neutrophil heterogeneity in humans remain unclear. We performed a comprehensive immunophenotypic and transcriptome analysis, at a bulk and single-cell level, of neutrophils from healthy donors and patients undergoing stress myelopoiesis upon exposure to growth factors, transplantation of hematopoietic stem cells (HSC-T), development of pancreatic cancer and viral infection. We uncover an extreme ersity of human neutrophils in vivo, reflecting the rates of cell mobilization, differentiation and exposure to environmental signals. Integrated control of developmental and inducible transcriptional programs linked flexible granulopoietic outputs with elicitation of stimulus-specific functional responses. In this context, we detected an acute interferon (IFN) response in the blood of patients receiving HSC-T that was mirrored by marked upregulation of IFN-stimulated genes in neutrophils but not in monocytes. Systematic characterization of human neutrophil plasticity may uncover clinically relevant biomarkers and support the development of diagnostic and therapeutic tools.
TNF Deficiency Fails to Protect BAFF Transgenic Mice against Autoimmunity and Reveals a Predisposition to B Cell Lymphoma
Publisher: The American Association of Immunologists
Date: 15-01-2004
DOI: 10.4049/JIMMUNOL.172.2.812
Abstract: TNF is well characterized as a mediator of inflammatory responses. TNF also facilitates organization of secondary lymphoid organs, particularly B cell follicles and germinal centers, a hallmark of T-dependent Ab responses. TNF also mediates defense against tumors. We examined the role of TNF in the development of inflammatory autoimmune disorders resembling systemic lupus erythematosus and Sjögren’s syndrome induced by excess B cell-activating factor belonging to the TNF family (BAFF), by generating BAFF-transgenic (Tg) mice lacking TNF. TNF−/− BAFF-Tg mice resembled TNF−/− mice, in that they lacked B cell follicles, follicular dendritic cells, and germinal centers, and have impaired responses to T-dependent Ags. Nevertheless, TNF−/− BAFF-Tg mice developed autoimmune disorders similar to that of BAFF-Tg mice. Disease in TNF−/− BAFF-Tg mice correlates with the expansion of transitional type 2 and marginal zone B cell populations and enhanced T-independent immune responses. TNF deficiency in BAFF-Tg mice also led to a surprisingly high incidence of B cell lymphomas (& %), which most likely resulted from the combined effects of BAFF promotion of neoplastic B cell survival, coupled with lack of protective antitumor defense by TNF. Thus, TNF appears to be dispensable for BAFF-mediated autoimmune disorders and may, in fact, counter any proneoplastic effects of high levels of BAFF in diseases such as Sjögren’s syndrome, systemic lupus erythematosus, and rheumatoid arthritis.
Ezh2 Controls Skin Tolerance through Distinct Mechanisms in Different Subsets of Skin Dendritic Cells
Publisher: Elsevier BV
Date: 12-2018
Peeking into the secret life of neutrophils
Publisher: No publisher found
Notch-dependent cooperativity between myeloid lineages promotes Langerhans cell histiocytosis pathology
Publisher: American Association for the Advancement of Science (AAAS)
Date: 23-12-2022
DOI: 10.1126/SCIIMMUNOL.ADD3330
Abstract: Langerhans cell histiocytosis (LCH) is a potentially fatal neoplasm characterized by the aberrant differentiation of mononuclear phagocytes, driven by mitogen-activated protein kinase (MAPK) pathway activation. LCH cells may trigger destructive pathology yet remain in a precarious state finely balanced between apoptosis and survival, supported by a unique inflammatory milieu. The interactions that maintain this state are not well known and may offer targets for intervention. Here, we used single-cell RNA-seq and protein analysis to dissect LCH lesions, assessing LCH cell heterogeneity and comparing LCH cells with normal mononuclear phagocytes within lesions. We found LCH discriminatory signatures pointing to senescence and escape from tumor immune surveillance. We also uncovered two major lineages of LCH with DC2- and DC3/monocyte-like phenotypes and validated them in multiple pathological tissue sites by high-content imaging. Receptor-ligand analyses and lineage tracing in vitro revealed Notch-dependent cooperativity between DC2 and DC3/monocyte lineages during expression of the pathognomonic LCH program. Our results present a convergent dual origin model of LCH with MAPK pathway activation occurring before fate commitment to DC2 and DC3/monocyte lineages and Notch-dependent cooperativity between lineages driving the development of LCH cells.
Multi-modal image cytometry approach – From dynamic to whole organ imaging
Publisher: Elsevier BV
Date: 10-2019
DOI: 10.1016/J.CELLIMM.2019.103946
Abstract: Optical imaging is a valuable tool to visualise biological processes in the context of the tissue. Each imaging modality provides the biologist with different types of information - cell dynamics and migration over time can be tracked with time-lapse imaging (e.g. intra-vital imaging) an overview of whole tissues can be acquired using optical clearing in conjunction with light sheet microscopy finer details such as cellular morphology and fine nerve tortuosity can be imaged at higher resolution using the confocal microscope. Multi-modal imaging combined with image cytometry - a form of quantitative analysis of image datasets - provides an objective basis for comparing between s le groups. Here, we provide an overview of technical aspects to look out for in an image cytometry workflow, and discuss issues related to s le preparation, image post-processing and analysis for intra-vital and whole organ imaging.
Nanocrystallization: A Unique Approach to Yield Bright Organic Nanocrystals for Biological Applications
Publisher: Wiley
Date: 02-11-2016
Abstract: A new bottom-up nanocrystallization method is developed to fabricate highly fluorescent organic nanocrystals in aqueous media using an aggregation-induced emission fluorogen (AIEgen) as an ex le. The nanocrystallization strategy leads to the fabrication of uniform nanocrystals of 110 ± 10 nm size in aqueous media, which shows over 400% increase in brightness as compared to the amorphous nanoaggregates.
Dimensionality reduction for visualizing single-cell data using UMAP
Publisher: Springer Science and Business Media LLC
Date: 03-12-2018
DOI: 10.1038/NBT.4314
Abstract: Advances in single-cell technologies have enabled high-resolution dissection of tissue composition. Several tools for dimensionality reduction are available to analyze the large number of parameters generated in single-cell studies. Recently, a nonlinear dimensionality-reduction technique, uniform manifold approximation and projection (UMAP), was developed for the analysis of any type of high-dimensional data. Here we apply it to biological data, using three well-characterized mass cytometry and single-cell RNA sequencing datasets. Comparing the performance of UMAP with five other tools, we find that UMAP provides the fastest run times, highest reproducibility and the most meaningful organization of cell clusters. The work highlights the use of UMAP for improved visualization and interpretation of single-cell data.
Understanding the Murine Cutaneous Dendritic Cell Network to Improve Intradermal Vaccination Strategies
Publisher: Springer Berlin Heidelberg
Date: 2010
DOI: 10.1007/82_2010_115
Abstract: Dendritic cells (DCs) form a heterogeneous group of antigen presenting cells that play different roles in tissue immunity. Recent studies have revealed the presence of distinct DC populations in murine skin, highlighting the complexity of the cutaneous DC network. In this review, we will define the major DC subsets that populate the different layers of the skin, focusing on their origin and the mechanisms controlling their homeostasis. We will also review recent evidence underlining the functional specialization of dermal DC subsets and its relevance in the design of novel vaccine approaches.
CD8 T Cells Regulate Allergic Contact Dermatitis by Modulating CCR2–Dependent TNF/iNOS–Expressing Ly6C + CD11b + Monocytic Cells
Publisher: Elsevier BV
Date: 03-2014
DOI: 10.1038/JID.2013.403
Abstract: Monocytes and their derived cells have critical roles in inflammation and immune defense. However, their function in skin diseases such as allergic contact dermatitis remains poorly defined. Using a model of contact hypersensitivity (CHS) toward 2,4-dinitrochlorobenzene, we show that Ly6C+ CD11b+ monocytic cells participate in the pathophysiology of CHS and their accumulation is regulated by effector CD8 T cells. These Ly6C+ CD11b+ monocytic cells are the primary contributors of tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS) and derive from Ly6C(hi)CCR2+ monocytes, as they were absent in non-inflamed skin and accumulate as a consequence of inflammation in a C-C chemokine receptor type 2 (CCR2)-dependent manner. Importantly, CCR2(-/-) mice, or wild-type mice depleted of monocytes via clodronate liposomes, display a marked decrease in TNF-α and iNOS expression accompanied by attenuated skin inflammation. Using transgenic mice and antibody depletion, we show that effector CD8 T cells regulate the accumulation of Ly6C+ CD11b+ monocytic cells through IL-17 and activate them for TNF-α and iNOS through IFN-γ. CD8 T cell-derived IFN-γ was also critical for the accumulation of the major histocompatibility complex II-expressing Ly6C+ CD11b+ subset, which expressed intermediate levels of CD11c and costimulatory molecules. Taken together, our findings provide further insight into the pathophysiology of allergic contact dermatitis by showing that CD8 T cells regulate the inflammatory cascade through TNF/iNOS-expressing Ly6C+ CD11b+ monocytic cells.
Technical Advance: Visualization of bone marrow monocyte mobilization using reporter mouse by multiphoton intravital microscopy
Publisher: No publisher found
Streamlining volumetric multi-channel image cytometry using hue-saturation-brightness-based surface creation
Publisher: Springer Science and Business Media LLC
Date: 06-09-2018
DOI: 10.1038/S42003-018-0139-Y
Abstract: Image cytometry is the process of converting image data to flow cytometry-style plots, and it usually requires computer-aided surface creation to extract out statistics for cells or structures. One way of dealing with structures stained with multiple markers in three-dimensional images, is carrying out multiple rounds of channel co-localization and image masking before surface creation, which is cumbersome and laborious. We propose the application of the hue-saturation-brightness color space to streamline this process, which produces complete surfaces, and allows the user to have a global view of the data before flexibly defining cell subsets. Spectral compensation can also be performed after surface creation to accurately resolve different signals. We demonstrate the utility of this workflow in static and dynamic imaging datasets of a needlestick injury on the mouse ear, and we believe this scalable and intuitive approach will improve the ease of performing histocytometry on biological s les.
A Three-Dimensional Atlas of Human Dermal Leukocytes, Lymphatics, and Blood Vessels
Publisher: Elsevier BV
Date: 04-2201
DOI: 10.1038/JID.2013.481
Developmental Analysis of Bone Marrow Neutrophils Reveals Populations Specialized in Expansion, Trafficking, and Effector Functions
Publisher: No publisher found
Intravital multiphoton imaging of immune responses in the mouse ear skin
Publisher: No publisher found
Hyaluronan Receptor LYVE-1-Expressing Macrophages Maintain Arterial Tone through Hyaluronan-Mediated Regulation of Smooth Muscle Cell Collagen
Publisher: Elsevier BV
Date: 12-2018
Research Techniques Made Simple: Optical Clearing and Three-Dimensional Volumetric Imaging of Skin Biopsies
Publisher: Elsevier BV
Date: 07-2020
Neutrophils guide pre-existing matrix into injured organs to initiate tissue repair
Publisher: Springer Science and Business Media LLC
Date: 30-03-2022
Visualizing the neutrophil response to sterile tissue injury in mouse dermis reveals a three-phase cascade of events
Publisher: Elsevier BV
Date: 10-2011
DOI: 10.1038/JID.2011.179
Abstract: Neutrophil granulocytes traffic into sites of organ injury in which they may not only participate in tissue repair and pathogen clearance but may also contribute to collateral cell damage through the release of noxious mediators. The dynamics and mechanisms of neutrophil migration in the extravascular space toward loci of tissue damage are not well understood. Here, we have used intravital multi-photon microscopy to dissect the behavior of neutrophils in response to tissue injury in the dermis of mice. We found that, following confined physical injury, initially rare scouting neutrophils migrated in a directional manner toward the damage focus. This was followed by the attraction of waves of additional neutrophils, and finally stabilization of the neutrophil cluster around the injury. Although neutrophil migration in the steady state and during the scouting phase depended on pertussis toxin-sensitive signals, the lification phase was sensitive to interference with the cyclic adenosine diphosphate ribose pathway. We finally demonstrated that neutrophil scouts also transit through the non-inflamed dermis, suggesting immunosurveillance function by these cells. Together, our data unravel a three-step cascade of events that mediates the specific accumulation of neutrophils at sites of sterile tissue injury in the interstitial space.
WDR82-binding long noncoding RNA lncEry controls mouse erythroid differentiation and maturation
Publisher: Rockefeller University Press
Date: 22-03-2022
DOI: 10.1084/JEM.20211688
Abstract: Hematopoietic differentiation is controlled by both genetic and epigenetic regulators. Long noncoding RNAs (lncRNAs) have been demonstrated to be important for normal hematopoiesis, but their function in erythropoiesis needs to be further explored. We profiled the transcriptomes of 16 murine hematopoietic cell populations by deep RNA sequencing and identified a novel lncRNA, Gm15915, that was highly expressed in erythroid-related progenitors and erythrocytes. For this reason, we named it lncEry. We also identified a novel lncEry isoform, which was the principal transcript that has not been reported before. lncEry depletion impaired erythropoiesis, indicating the important role of the lncRNA in regulating erythroid differentiation and maturation. Mechanistically, we found that lncEry interacted with WD repeat–containing protein 82 (WDR82) to promote the transcription of Klf1 and globin genes and thus control the early and late stages of erythropoiesis, respectively. These findings identified lncEry as an important player in the transcriptional regulation of erythropoiesis.
Capturing the Fantastic Voyage of Monocytes Through Time and Space
Publisher: No publisher found
Neutrophil mobilization via plerixafor-mediated CXCR4 inhibition arises from lung demargination and blockade of neutrophil homing to the bone marrow
Publisher: No publisher found
NIR-II Excitable Conjugated Polymer Dots with Bright NIR-I Emission for Deep In Vivo Two-Photon Brain Imaging Through Intact Skull
Publisher: No publisher found
Heterogeneity of neutrophils
Publisher: No publisher found
Illuminating the covert mission of mononuclear phagocytes in their regional niches
Publisher: No publisher found
3-Dimensional Optical Clearing and Imaging of Pruritic Atopic Dermatitis and Psoriasis Skin Reveals Downregulation of Epidermal Innervation
Publisher: No publisher found
Anti-Allergic Inflammatory Activity of Interleukin-37 Is Mediated by Novel Signaling Cascades in Human Eosinophils
Publisher: Frontiers Media SA
Date: 22-06-2018
Inducing Ischemia-reperfusion Injury in the Mouse Ear Skin for Intravital Multiphoton Imaging of Immune Responses
Publisher: MyJove Corporation
Date: 22-12-2016
DOI: 10.3791/54956
Hyaluronan Receptor LYVE-1-Expressing Macrophages Maintain Arterial Tone through Hyaluronan-Mediated Regulation of Smooth Muscle Cell Collagen(vol 49, 326, 2018)
Publisher: No publisher found
B cell-activating factor belonging to the TNF family (BAFF)-R is the principal BAFF receptor facilitating BAFF costimulation of circulating T and B cells
Publisher: The American Association of Immunologists
Date: 15-07-2004
DOI: 10.4049/JIMMUNOL.173.2.807
Abstract: BAFF (B cell-activating factor belonging to the TNF family) is a cell survival and maturation factor for B cells, and overproduction of BAFF is associated with systemic autoimmune disease. BAFF binds to three receptors, BAFF-R, transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI), and B cell maturation Ag (BCMA). Using specific mAbs, BAFF-R was found to be the predominant BAFF receptor expressed on peripheral B cells, in both humans and mice, and antagonist mAbs to BAFF-R blocked BAFF-mediated costimulation of anti-μ responses. The other BAFF receptors showed a much more restricted expression pattern, suggestive of specialized roles. BCMA was expressed by germinal center B cells, while TACI was expressed predominantly by splenic transitional type 2 and marginal zone B cells, as well as activated B cells, but was notably absent from germinal center B cells. BAFF was also an effective costimulator for T cells, and this costimulation occurs entirely through BAFF-R. BAFF-R, but not TACI or BCMA, was expressed on activated/memory subsets of T cells, and T cells from BAFF-R mutant A/WySnJ mice failed to respond to BAFF costimulation. Thus, BAFF-R is important not only for splenic B cell maturation, but is the major mediator of BAFF-dependent costimulatory responses in peripheral B and T cells.
Transitional premonocytes emerge in the periphery for host defense against bacterial infections
Publisher: American Association for the Advancement of Science (AAAS)
Date: 04-03-2022
Abstract: Circulating Ly6C hi monocytes often undergo cellular death upon exhaustion of their antibacterial effector functions, which limits their capacity for subsequent macrophage differentiation. This shrouds the understanding on how the host replaces the tissue-resident macrophage niche effectively during bacterial invasion to avert infection morbidity. Here, we show that proliferating transitional premonocytes (TpMos), an immediate precursor of mature Ly6C hi monocytes (MatMos), were mobilized into the periphery in response to acute bacterial infection and sepsis. TpMos were less susceptible to apoptosis and served as the main source of macrophage replenishment when MatMos were vulnerable toward bacteria-induced cellular death. Furthermore, TpMo and its derived macrophages contributed to host defense by balancing the proinflammatory cytokine response of MatMos. Consequently, adoptive transfer of TpMos improved the survival outcome of lethal sepsis. Our findings hence highlight a protective role for TpMos during bacterial infections and their contribution toward monocyte-derived macrophage heterogeneity in distinct disease outcomes.
Visualizing the Neutrophil Response to Sterile Tissue Injury in Mouse Dermis Reveals a Three-Phase Cascade of Events
Publisher: No publisher found
Nanocrystallization: A Unique Approach to Yield Bright Organic Nanocrystals for Biological Applications
Publisher: No publisher found
NIR‐II Excitable Conjugated Polymer Dots with Bright NIR‐I Emission for Deep In Vivo Two‐Photon Brain Imaging Through Intact Skull
Publisher: Wiley
Date: 21-01-2019
BAFF augments certain Th1-associated inflammatory responses
Publisher: No publisher found
Dengue virus–elicited tryptase induces endothelial permeability and shock
Publisher: American Society for Clinical Investigation
Date: 26-08-2019
DOI: 10.1172/JCI128426
Red Emissive Biocompatible Nanoparticles from Tetraphenylethene‐Decorated BODIPY Luminogens for Two‐Photon Excited Fluorescence Cellular Imaging and Mouse Brain Blood Vascular Visualization
Publisher: Wiley
Date: 21-10-2013
Fate Mapping Analysis Reveals That Adult Microglia Derive from Primitive Macrophages
Publisher: No publisher found
BAFF costimulation of Toll‐like receptor‐activatedB‐1 cells
Publisher: Wiley
Date: 30-06-2006
Abstract: B cell-activating factor belonging to the TNF family (BAFF) and its receptor BAFF-R play critical roles in the maturation and survival of conventional peripheral B cells. However, they appeared to be dispensable for the generation and maintenance of CD5(+) B-1 cells as BAFF(-/-) and BAFF-R(-/-) mice have normal B-1 cell populations. Hence, it is presently unclear if B-1 cells are responsive to BAFF and if BAFF regulates some aspects of B-1 cell function. We show here that BAFF-R and transmembrane activator and CAML interactor (TACI) are the major receptors expressed by B-1 cells. Specifically, we show that BAFF treatment of B-1 cells leads to increased NF-kappaB p100 processing and CD21/CD35 expression. Interestingly, toll-like receptor (TLR) engagement of B-1 cells augmented the surface expression of BAFF receptors and rendered them responsive to BAFF costimulation, as evidenced by their increased proliferation, expression of cell surface activation markers and secretion of the pro-inflammatory cytokine IL-6 and the anti-inflammatory cytokine IL-10. This costimulatory effect is achieved primarily through BAFF-R as BAFF failed to costimulate B-1 cells obtained from A/WySnJ mice which have defective BAFF-R signaling. Thus, as TLR are innate immune receptors and B-1 cells are "innate-like" lymphocytes, our data provide evidence that BAFF plays a role in innate immunity.
Biocompatible Green and Red Fluorescent Organic Dots with Remarkably Large Two-Photon Action Cross Sections for Targeted Cellular Imaging and Real-Time Intravital Blood Vascular Visualization
Publisher: No publisher found
Perivascular leukocyte clusters are essential for efficient activation of effector T cells in the skin
Publisher: Springer Science and Business Media LLC
Date: 21-09-2014
DOI: 10.1038/NI.2992
Abstract: It remains largely unclear how antigen-presenting cells (APCs) encounter effector or memory T cells efficiently in the periphery. Here we used a mouse contact hypersensitivity (CHS) model to show that upon epicutaneous antigen challenge, dendritic cells (DCs) formed clusters with effector T cells in dermal perivascular areas to promote in situ proliferation and activation of skin T cells in a manner dependent on antigen and the integrin LFA-1. We found that DCs accumulated in perivascular areas and that DC clustering was abrogated by depletion of macrophages. Treatment with interleukin 1α (IL-1α) induced production of the chemokine CXCL2 by dermal macrophages, and DC clustering was suppressed by blockade of either the receptor for IL-1 (IL-1R) or the receptor for CXCL2 (CXCR2). Our findings suggest that the dermal leukocyte cluster is an essential structure for elicitating acquired cutaneous immunity.
Perivascular leukocyte clusters are essential for efficient activation of effector T cells in the skin
Publisher: No publisher found
DOI: 10.1038/NI.2992}
Langerhans cells are precommitted to immune tolerance induction
Publisher: Proceedings of the National Academy of Sciences
Date: 17-10-2011
Abstract: Antigen-dependent interactions between T lymphocytes and dendritic cells (DCs) can produce two distinct outcomes: tolerance and immunity. It is generally considered that all DC subsets are capable of supporting both tolerogenic and immunogenic responses, depending on their exposure to activating signals. Here, we tested whether epidermal Langerhans cells (LCs) can support immunogenic responses in vivo in the absence of antigen presentation by other DC subsets. CD4 T cells responding to antigen presentation by activated LCs initially proliferated but then failed to differentiate into effector/memory cells or to survive long term. The tolerogenic function of LCs was maintained after exposure to potent adjuvants and occurred despite up-regulation of the costimulatory molecules CD80, CD86, and IL-12, but was consistent with their failure to translocate the NF-κB family member RelB from the cytoplasm to the nucleus. Commitment of LCs to tolerogenic function may explain why commensal microorganisms expressing Toll-like receptor (TLR) ligands but confined to the skin epithelium are tolerated, whereas invading pathogens that breach the epithelial basement membrane and activate dermal DCs stimulate a strong immune response.
CD8 T Cells Regulate Allergic Contact Dermatitis by Modulating CCR2-Dependent TNF/iNOS-Expressing Ly6C(+)CD11b(+) Monocytic Cells
Publisher: No publisher found
Rodent Plasmodium-infected red blood cells: Imaging their fates and interactions within their hosts
Publisher: No publisher found
Developmental Analysis of Bone Marrow Neutrophils Reveals Populations Specialized in Expansion, Trafficking, and Effector Functions
Publisher: Elsevier BV
Date: 02-2018
DOI: 10.1016/J.IMMUNI.2018.02.002
Abstract: Neutrophils are specialized innate cells that require constant replenishment from proliferative bone marrow (BM) precursors as a result of their short half-life. Although it is established that neutrophils are derived from the granulocyte-macrophage progenitor (GMP), the differentiation pathways from GMP to functional mature neutrophils are poorly defined. Using mass cytometry (CyTOF) and cell-cycle-based analysis, we identified three neutrophil subsets within the BM: a committed proliferative neutrophil precursor (preNeu) which differentiates into non-proliferating immature neutrophils and mature neutrophils. Transcriptomic profiling and functional analysis revealed that preNeu require the C/EBPε transcription factor for their generation from the GMP, and their proliferative program is substituted by a gain of migratory and effector function as they mature. preNeus expand under microbial and tumoral stress, and immature neutrophils are recruited to the periphery of tumor-bearing mice. In summary, our study identifies specialized BM granulocytic populations that ensure supply under homeostasis and stress responses.
DC mobilization from the skin requires docking to immobilized CCL21 on lymphatic endothelium and intralymphatic crawling
Publisher: Rockefeller University Press
Date: 19-09-2011
DOI: 10.1084/JEM.20102392
Abstract: Dendritic cells (DCs) must travel through lymphatics to carry skin antigens into lymph nodes. The processes controlling their mobilization and migration have not been completely delineated. We studied how DCs in live mice respond to skin inflammation, transmigrate through lymphatic endothelium, and propagate in initial lymphatics. At steady state, dermal DCs remain sessile along blood vessels. Inflammation mobilizes them, accelerating their interstitial motility 2.5-fold. CCR7-deficient BMDCs crawl as fast as wild-type DCs but less persistently. We observed discrete depositions of CCL21 complexed with collagen-IV on the basement membrane of initial lymphatics. Activated DCs move directionally toward lymphatics, contact CCL21 puncta, and migrate through portals into the lumen. CCR7-deficient DCs arrive at lymphatics through random migration but fail to dock and transmigrate. Once inside vessels, wild-type DCs use lamellipodia to crawl along lymphatic endothelium and, sensing lymph flow, proceed downstream. DCs start drifting freely only in collecting lymphatics. These results demonstrate in vivo that the CCL21–CCR7 axis plays a dual role in DC mobilization: promoting both chemotaxis and arrest of DCs on lymphatic endothelium. Intralymphatic crawling, in which DCs combine active adhesion-based migration and directional cues from lymph flow, represents a new step in DC mobilization which may be amenable to regulation.
Development of nephritis but not sialadenitis in autoimmune-prone BAFF transgenic mice lacking marginal zone B cells
Publisher: No publisher found
CD44 Mediates Successful Interstitial Navigation by Killer T Cells and Enables Efficient Antitumor Immunity
Publisher: No publisher found
Reprint of “Multi-modal image cytometry approach – From dynamic to whole organ imaging”
Publisher: Elsevier BV
Date: 04-2020
Ezh2 Controls Skin Tolerance through Distinct Mechanisms in Different Subsets of Skin Dendritic Cells
Publisher: No publisher found
Real-Time Imaging of Dendritic Cell Responses to Sterile Tissue Injury
Publisher: No publisher found
Whole blood immunophenotyping uncovers immature neutrophil-to-VD2 T-cell ratio as an early marker for severe COVID-19
Publisher: Springer Science and Business Media LLC
Date: 16-10-2020
DOI: 10.1038/S41467-020-19080-6
Abstract: SARS-CoV-2 is the novel coronavirus responsible for the current COVID-19 pandemic. Severe complications are observed only in a small proportion of infected patients but the cellular mechanisms underlying this progression are still unknown. Comprehensive flow cytometry of whole blood s les from 54 COVID-19 patients reveals a dramatic increase in the number of immature neutrophils. This increase strongly correlates with disease severity and is associated with elevated IL-6 and IP-10 levels, two key players in the cytokine storm. The most pronounced decrease in cell counts is observed for CD8 T-cells and VD2 γδ T-cells, which both exhibit increased differentiation and activation. ROC analysis reveals that the count ratio of immature neutrophils to VD2 (or CD8) T-cells predicts pneumonia onset (0.9071) as well as hypoxia onset (0.8908) with high sensitivity and specificity. It would thus be a useful prognostic marker for preventive patient management and improved healthcare resource management.
CD 41 is a reliable identification and activation marker for murine basophils in the steady state and during helminth and malarial infections
Publisher: Wiley
Date: 10-04-2014
Abstract: Basophils, a rare leukocyte population in peripheral circulation, are conventionally identified as CD45(int) CD49b(+) FcεRI(+) cells. Here, we show that basophils from blood and several organs of naïve wild-type mice express CD41, the α subunit of α(IIb)β₃ integrin. CD41 expression on basophils is upregulated after in vivo IL-3 treatment and during infection with Nippostrongylus brasiliensis (Nb). Moreover, CD41 can be used as a reliable marker for basophils, circumventing technical difficulties associated with FcεRI for basophil identification in a Nb infection model. In vitro anti-IgE cross-linking and IL-3 basophil stimulation showed that CD41 upregulation positively correlates with augmented surface expression of CD200R and increased production of IL-4/IL-13, indicating that CD41 is a basophil activation marker. Furthermore, we found that infection with Plasmodium yoelii 17X (Py17x) induced a profound basophilia and using Mcpt8(DTR) reporter mice as a basophil-specific depletion model, we verified that CD41 can be used as a marker to track basophils in the steady state and during infection. During malarial infection, CD41 expression on basophils is negatively regulated by IFN-γ and positively correlates with increased basophil IL-4 production. In conclusion, we provide evidence that CD41 can be used as both an identification and activation marker for basophils during homeostasis and immune challenge.
TNF deficiency fails to protect BAFF transgenic mice against autoimmunity and reveals a predisposition to B cell lymphoma
Publisher: No publisher found
PD-L1 expression on nonclassical monocytes reveals their origin and immunoregulatory function
Publisher: American Association for the Advancement of Science (AAAS)
Date: 07-06-2019
DOI: 10.1126/SCIIMMUNOL.AAR3054
Abstract: PD-L1 + Ly6C lo monocytes derive from Ly6C hi monocytes in bone marrow and control T cell survival in tertiary lymphoid organs.
A Small‐Molecule FRET Reporter for the Real‐Time Visualization of Cell‐Surface Proteolytic Enzyme Functions
Publisher: Wiley
Date: 27-10-2014
Abstract: Real-time imaging of cell-surface-associated proteolytic enzymes is critical to better understand their performances in both physiological and pathological processes. However, most current approaches are limited by their complexity and poor membrane-anchoring properties. Herein, we have designed and synthesized a unique small-molecule fluorescent probe, which combines the principles of passive exogenous membrane insertion and Förster resonance energy transfer (FRET) to image cell-surface-localized furin-like convertase activities. The membrane-associated furin-like enzymatic cleavage of the peptide probe leads to an increased fluorescence intensity which was mainly localized on the plasma membrane of the furin-expressed cells. This small-molecule fluorescent probe may serve as a unique and reliable reporter for real-time visualization of endogenous cell-surfaceassociated proteolytic furin-like enzyme functions in live cells and tissues using one-photon and two-photon microscopy.
Perivascular macrophages mediate neutrophil recruitment during bacterial skin infection
Publisher: Springer Science and Business Media LLC
Date: 24-11-2014
DOI: 10.1038/NI.2769
Two distinct interstitial macrophage populations coexist across tissues in specific subtissular niches
Publisher: American Association for the Advancement of Science (AAAS)
Date: 15-03-2019
Abstract: Resident tissue macrophages (RTMs) reside in various tissue-specific niches during development. They evince microenvironment-directed phenotypes that support host defense and tissue homeostasis. Chakarov et al. used single-cell RNA sequencing and fate-mapping of murine lung RTMs to interrogate RTM-subset heterogeneity, interrelationships, and ontogeny (see the Perspective by Mildner and Yona). In addition to alveolar macrophages, they identified two different interstitial macrophage populations. One population mostly abutted nerve fibers the other population preferentially localized near blood vessels and appeared to support vessel integrity and inhibit inflammatory cell infiltration into tissues. Science , this issue p. eaau0964 see also p. 1154
CD44 Mediates Successful Interstitial Navigation by Killer T Cells and Enables Efficient Antitumor Immunity
Publisher: Elsevier BV
Date: 06-2008
Cutaneous immunosurveillance by self-renewing dermal gamma delta T cells
Publisher: No publisher found
Targeted induction of antigen expression within dendritic cells modulates antigen-specific immunity afforded by recombinant BCG
Publisher: Elsevier BV
Date: 02-2011
DOI: 10.1016/J.VACCINE.2010.12.070
Abstract: The targeted modulation of antigen expression by recombinant vaccine vehicles would significantly aid development of effective immunotherapeutic strategies. In this report we demonstrate that the Mycobacterium tuberculosis hspX promoter can be used to regulate in vivo induction of antigens expressed by recombinant Bacille Calmette Guérin (rBCG). HspX promoter induction occurred rapidly upon entry of rBCG into cultured dendritic cells (DCs), as evidenced by GFP levels in DCs when infected with BCG:P(hspX)-GFP, in which P(hspX) controlled GFP expression. Vaccination of mice with BCG:P(hspX)-GFP led to rapid in vivo induction of GFP associated with an influx of GFP(+) DCs at the infection site. P(hspX)-driven antigen expression resulted in an improved capacity of DCs to prime antigen-specific T cells, as infection of DCs with BCG:P(hspX)-85B, where the hspX promoter controls expression of M. tuberculosis Ag85B, led to enhanced proliferation of Ag85B-reactive CD4(+) T cells compared to BCG overexpressing Ag85B using the strong Mycobacterium bovis hsp60 promoter. This enhancement of rBCG-induced immunity was also evident in vivo mice vaccinated with BCG:P(hspX)-85B displayed markedly improved generation of Ag85B-reactive IFN-γ-secreting T cells compared to control BCG-vaccinated mice, which was most pronounced at extended times points post-vaccination. These data reveal a novel strategy to enhance the development and maintenance of vaccine-specific T cell responses.
Biocompatible nanoparticles based on diketo-pyrrolo-pyrrole (DPP) with aggregation-induced Red/NIR emission for in vivo two-photon fluorescence imaging
Publisher: Wiley
Date: 30-03-2015
In silico modeling of cancer cell dissemination and metastasis
Publisher: Wiley
Date: 05-2013
DOI: 10.1111/NYAS.12077
Abstract: Metastasis is the main cause of cancer-related death. It is surprising then that the exact nature of metastasis-the process by which cancer cells leave the primary tumor to reach distant organs, and resume proliferation-is not fully understood. Moreover, the different conditions under which the immune system can either promote or suppress metastasis are only now beginning to be uncovered. In recent years, our understanding of metastasis as a genocentric, cell-autonomous process has shifted toward a systemic model in which interactions between cancer cells and their surrounding microenvironments lead to dissemination and metastasis. In silico modeling of the various steps involved in metastasis can help provide an understanding of how tumor properties emerge from the complex interplays between tumor cells and their microenvironment. In silico models can also be useful in identifying the selective forces that favor the outcomes of cancer cells with metastatic potential.
Two‐photon imaging of effector T‐cell behavior: lessons from a tumor model
Publisher: Wiley
Date: 02-2008
PD-L1 expression on nonclassical monocytes reveals their origin and immunoregulatory function
Publisher: No publisher found
Rodent Plasmodium-infected red blood cells: Imaging their fates and interactions within their hosts
Publisher: Elsevier BV
Date: 02-2014
DOI: 10.1016/J.PARINT.2013.07.012
Abstract: Malaria, a disease caused by the Plasmodium parasite, remains one of the most deadly infectious diseases known to mankind. The parasite has a complex life cycle, of which only the erythrocytic stage is responsible for the erse pathologies induced during infection. To date, the disease mechanisms that underlie these pathologies are still poorly understood. In the case of infections caused by Plasmodium falciparum, the species responsible for most malaria related deaths, pathogenesis is thought to be due to the sequestration of infected red blood cells (IRBCs) in deep tissues. Other human and rodent malaria parasite species are also known to exhibit sequestration. Here, we review the different techniques that allow researchers to study how rodent malaria parasites modify their host cells, the distribution of IRBCs in vivo as well as the interactions between IRBCs and host tissues.
Bright AIEgen-Protein Hybrid Nanocomposite for Deep and High-Resolution In Vivo Two-Photon Brain Imaging
Publisher: No publisher found
The impact of ischemia‐reperfusion injuries on skin resident murine dendritic cells
Publisher: Wiley
Date: 23-03-2018
Abstract: Pressure ulcers are a chronic problem for patients or the elderly who require extended periods of bed rest. The formation of ulcers is due to repeated cycles of ischemia-reperfusion (IR), which initiates an inflammatory response. Advanced ulcers disrupt the skin barrier, resulting in further complications. To date, the immunological aspect of skin IR has been understudied, partly due to the complexity of the skin immune cells. Through a combination of mass cytometry, confocal imaging and intravital multiphoton imaging, this study establishes a workflow for multidimensionality single cell analysis of skin myeloid cell responses in the context of IR injury with high spatiotemporal resolution. The data generated has provided us with previously uncharacterized insights into the distinct cellular behavior of resident dendritic cells (DCs) and recruited neutrophils post IR. Of interest, we observed a drop in DDC numbers in the IR region, which was subsequently replenished 48h post IR. More importantly, in these cells, we observe an attenuated response to repeated injuries, which may have implications in the subsequent wound healing process.
Neutrophil mobilization via plerixafor-mediated CXCR4 inhibition arises from lung demargination and blockade of neutrophil homing to the bone marrow
Publisher: Rockefeller University Press
Date: 30-09-2013
DOI: 10.1084/JEM.20130056
Abstract: Blood neutrophil homeostasis is essential for successful host defense against invading pathogens. Circulating neutrophil counts are positively regulated by CXCR2 signaling and negatively regulated by the CXCR4–CXCL12 axis. In particular, G-CSF, a known CXCR2 signaler, and plerixafor, a CXCR4 antagonist, have both been shown to correct neutropenia in human patients. G-CSF directly induces neutrophil mobilization from the bone marrow (BM) into the blood, but the mechanisms underlying plerixafor-induced neutrophilia remain poorly defined. Using a combination of intravital multiphoton microscopy, genetically modified mice and novel in vivo homing assays, we demonstrate that G-CSF and plerixafor work through distinct mechanisms. In contrast to G-CSF, CXCR4 inhibition via plerixafor does not result in neutrophil mobilization from the BM. Instead, plerixafor augments the frequency of circulating neutrophils through their release from the marginated pool present in the lung, while simultaneously preventing neutrophil return to the BM. Our study demonstrates for the first time that drastic changes in blood neutrophils can originate from alternative reservoirs other than the BM, while implicating a role for CXCR4–CXCL12 interactions in regulating lung neutrophil margination. Collectively, our data provides valuable insights into the fundamental regulation of neutrophil homeostasis, which may lead to the development of improved treatment regimens for neutropenic patients.
Neutrophil: A mobile fertilizer
Publisher: Rockefeller University Press
Date: 19-12-2018
DOI: 10.1084/JEM.20182059
Abstract: In this issue of JEM, Lee et al. (0.1084/jem.20181170) provide evidence to show that early influx of neutrophils into omentum represents a key mechanism in establishing the premetastatic niche for the subsequent implantation of ovarian cancer cells at this site.
Micelle/Silica Co-protected Conjugated Polymer Nanoparticles for Two-Photon Excited Brain Vascular Imaging
Publisher: No publisher found
DOI: 10.1021/CM4040374}
Peeking into the secret life of neutrophils
Publisher: Springer Science and Business Media LLC
Date: 11-03-2201
DOI: 10.1007/S12026-012-8292-8
Abstract: The migration of neutrophils between tissue compartments is an important aspect of innate immune surveillance. This process is regulated by a cascade of cellular and molecular signals to avoid unnecessary crowding of neutrophils at the periphery, to allow rapid mobilization of neutrophils in response to inflammatory stimuli, and to return to a state of homeostasis after the response. Intravital microscopy approaches have been fundamental in unraveling many aspects of neutrophil behavior, providing important mechanistic information on the processes involved in basal and disease states. Here, we provide a broad overview of the current state of research on neutrophil biology, describing the processes in the typical life cycle of neutrophils, from their first appearance in the bone marrow until their eventual destruction. We will focus on novel aspects of neutrophil behavior, which had previously been elusive until their recent elucidation by advanced intravital microscopy techniques.
Dual modal ultra-bright nanodots with aggregation-induced emission and gadolinium-chelation for vascular integrity and leakage detection
Publisher: No publisher found
Lights, camera, and action: vertebrate skin sets the stage for immune cell interaction with arthropod-vectored pathogens.
Publisher: Frontiers Media SA
Date: 2013
Neutrophil: A mobile fertilizer
Publisher: No publisher found
BAFF augments certain Th1-associated inflammatory responses
Publisher: The American Association of Immunologists
Date: 05-2005
DOI: 10.4049/JIMMUNOL.174.9.5537
Abstract: B cell-activating factor belonging to the TNF family (BAFF BLyS) is a critical regulator of B cell maturation and survival, and its overexpression in BAFF transgenic (Tg) mice results in the development of autoimmune disorders. BAFF also affects T cell function through binding to one of the BAFF receptors, BAFF-R. Using BAFF Tg mice, we examined a typical Th1-mediated response, the cutaneous delayed-type hypersensitivity reaction, and found a much greater degree of paw swelling and inflammation than in control mice. Importantly, delayed-type hypersensitivity scores correlated directly with BAFF levels in serum. Conversely, in a Th2-mediated model of allergic airway inflammation, BAFF Tg mice were largely protected and showed markedly reduced Ag-specific T cell proliferation and eosinophil infiltration associated with the airways. Thus, local and/or systemically distributed BAFF affects Th1 and Th2 responses and impacts on the course of some T cell-mediated inflammatory reactions. Our results are consistent with the idea that BAFF augments T cell as well as B cell responses, particularly Th1-type responses. Results in BAFF Tg mice may reflect the situation in certain autoimmune patients or virally infected in iduals, because BAFF levels in blood are comparable.
Polymerization-Enhanced Two-Photon Photosensitization for Precise Photodynamic Therapy
Publisher: American Chemical Society (ACS)
Date: 14-02-2019
Abstract: Two-photon excited photodynamic therapy (2PE-PDT) has attracted great attention in recent years due to its great potential for deep-tissue and highly spatiotemporally precise cancer therapy. Photosensitizers (PSs) with high singlet oxygen (
CD41 is a reliable identification and activation marker for murine basophils in the steady state and during helminth and malarial infections
Publisher: No publisher found
A Small-Molecule FRET Reporter for the Real-Time Visualization of Cell-Surface Proteolytic Enzyme Functions
Publisher: No publisher found
A Liver Capsular Network of Monocyte-Derived Macrophages Restricts Hepatic Dissemination of Intraperitoneal Bacteria by Neutrophil Recruitment
Publisher: Elsevier BV
Date: 08-2017
DOI: 10.1016/J.IMMUNI.2017.07.018
Abstract: The liver is positioned at the interface between two routes traversed by pathogens in disseminating infection. Whereas blood-borne pathogens are efficiently cleared in hepatic sinusoids by Kupffer cells (KCs), it is unknown how the liver prevents dissemination of peritoneal pathogens accessing its outer membrane. We report here that the hepatic capsule harbors a contiguous cellular network of liver-resident macrophages phenotypically distinct from KCs. These liver capsular macrophages (LCMs) were replenished in the steady state from blood monocytes, unlike KCs that are embryonically derived and self-renewing. LCM numbers increased after weaning in a microbiota-dependent process. LCMs sensed peritoneal bacteria and promoted neutrophil recruitment to the capsule, and their specific ablation resulted in decreased neutrophil recruitment and increased intrahepatic bacterial burden. Thus, the liver contains two separate and non-overlapping niches occupied by distinct resident macrophage populations mediating immunosurveillance at these two pathogen entry points to the liver.
Biocompatible Nanoparticles Based on Diketo-Pyrrolo-Pyrrole (DPP) with Aggregation-Induced Red/NIR Emission for In Vivo Two-Photon Fluorescence Imaging
Publisher: No publisher found
B cell-activating factor belonging to the TNF family acts through separate receptors to support B cell survival and T cell-independent antibody formation
Publisher: No publisher found
Biocompatible green and red fluorescent organic dots with remarkably large two-photon action cross sections for targeted cellular imaging and real-time intravital blood vascular visualization
Publisher: American Chemical Society (ACS)
Date: 02-07-2015
In vivo label‐free functional photoacoustic monitoring of ischemic reperfusion
Publisher: Wiley
Date: 04-2019
Abstract: Pressure ulcer formation is a common problem among patients confined to bed or restricted to wheelchairs. The ulcer forms when the affected skin and underlying tissues go through repeated cycles of ischemia and reperfusion, leading to inflammation. This theory is evident by intravital imaging studies performed in immune cell-specific, fluorescent reporter mouse skin with induced ischemia-reperfusion (I-R) injuries. However, traditional confocal or multiphoton microscopy cannot accurately monitor the progression of vascular reperfusion by contrast agents, which leaks into the interstitium under inflammatory conditions. Here, we develop a dual-wavelength micro electro mechanical system (MEMS) scanning-based optical resolution photoacoustic microscopy (OR-PAM) system for continuous label-free functional imaging of vascular reperfusion in an IR mouse model. This MEMS-OR-PAM system provides fast scanning speed for concurrent dual-wavelength imaging, which enables continuous monitoring of the reperfusion process. During reperfusion, the revascularization of blood vessels and the oxygen saturation (sO
A Liver Capsular Network of Monocyte-Derived Macrophages Restricts Hepatic Dissemination of Intraperitoneal Bacteria by Neutrophil Recruitment
Publisher: No publisher found
Micelle/Silica Co-protected Conjugated Polymer Nanoparticles for Two-Photon Excited Brain Vascular Imaging
Publisher: American Chemical Society (ACS)
Date: 26-02-2014
DOI: 10.1021/CM4040374
In vivo Imaging of Cutaneous T-Cell Lymphoma Migration to the Skin
Publisher: No publisher found
Inducing Ischemia-reperfusion Injury in the Mouse Ear Skin for Intravital Multiphoton Imaging of Immune Responses
Publisher: No publisher found
DOI: 10.3791/54956}
Dimensionality reduction for visualizing single-cell data using UMAP
Publisher: No publisher found
DOI: 10.1038/NBT.4314}
Silole-Based Red Fluorescent Organic Dots for Bright Two-Photon Fluorescence In vitro Cell and In vivo Blood Vessel Imaging
Publisher: No publisher found
Efficient aortic lymphatic drainage is necessary for atherosclerosis regression induced by ezetimibe
Publisher: American Association for the Advancement of Science (AAAS)
Date: 11-12-2020
Abstract: The results show that a functional lymphatic drainage of the aorta is critical to inhibit atherosclerosis progression and mediate its regression.
Intravital multiphoton imaging of immune responses in the mouse ear skin
Publisher: Springer Science and Business Media LLC
Date: 12-01-2012
Abstract: Multiphoton (MP) microscopy enables the direct in vivo visualization, with high spatial and temporal resolution, of fluorescently tagged immune cells, extracellular matrix and vasculature in tissues. This approach, therefore, represents a powerful alternative to traditional methods of assessing immune cell function in the skin, which are mainly based on flow cytometry and histology. Here we provide a step-by-step protocol describing experimental procedures for intravital MP imaging of the mouse ear skin, which can be easily adapted to address many specific skin-related biological questions. We demonstrate the use of this procedure by characterizing the response of neutrophils during cutaneous inflammation, which can be used to perform in-depth analysis of neutrophil behavior in the context of the skin microanatomy, including the epidermis, dermis and blood vessels. Such experiments are typically completed within 1 d, but as the procedures are minimally invasive, it is possible to perform longitudinal studies through repeated imaging.
Migratory Dermal Dendritic Cells Act as Rapid Sensors of Protozoan Parasites
Publisher: Public Library of Science (PLoS)
Date: 28-11-2008
Organic nanoparticles with ultrahigh quantum yield and aggregation-induced emission characteristics for cellular imaging and real-time two-photon lung vasculature imaging
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C8TB00386F
Abstract: Organic nanoparticles with a high quantum yield of 90% and aggregation-induced emission characteristics were prepared for cellular imaging and real-time two-photon vasculature imaging of the lungs.
Dynamic Imaging of CD8+ T Cells and Dendritic Cells during Infection with Toxoplasma gondii
Publisher: Public Library of Science (PLoS)
Date: 03-07-2009
A quantitative approach to histopathological dissection of elastin-related disorders using multiphoton microscopy
Publisher: Oxford University Press (OUP)
Date: 10-2013
DOI: 10.1111/BJD.12430
Abstract: Multiphoton microscopy (MPM) is a novel imaging technology that has recently become applicable for diagnostic purposes. The use of (near) infrared light in MPM allows for deep tissue imaging. In addition, this modality exploits the autofluorescent nature of extracellular matrix fibres within the skin. To quantitate the structure and abundance of elastic fibres in human dermis in three dimensions utilizing autofluorescent signals generated by MPM for the objective examination of elastin-related skin disorders. Cross-sections of skin s les from elastin-related disorders were analysed by MPM and correlated to histopathology. In situ visualization of elastic fibres by MPM was conducted by en face imaging of ex vivo skin s les through the intact epidermis. Image analysis software was used to quantify elastic fibres in three dimensions. Based on the MPM-detected elastin-specific autofluorescence, we developed the Dermal Elastin Morphology Index (DEMI), calculated as the ratio of elastic fibre surface area and volume. This enabled objective three-dimensional quantification of elastic fibres. Quantitative scoring of sun-damaged skin using DEMI correlated with qualitative histopathological grading of the severity of solar elastosis. Furthermore, this approach was applied to changes in elastic fibre architecture in other disorders, such as pseudoxanthoma elasticum (PXE), PXE-like syndrome, elastofibroma, focal dermal elastosis, anetoderma, mid-dermal elastolysis and striae distensae. We imaged elastic fibres in intact ex vivo skin imaged en face through the epidermis, indicating that this approach could be used in vivo. MPM has the potential for noninvasive in vivo visualization of elastic fibres in the dermis with near histological resolution. DEMI allows objective assessment of elastic fibres to support diagnosis and monitoring of disease progress or therapy of elastin-related skin disorders.
DC mobilization from the skin requires docking to immobilized CCL21 on lymphatic endothelium and intralymphatic crawling
Publisher: No publisher found
In vivo Imaging of Cutaneous T-Cell Lymphoma Migration to the Skin
Publisher: American Association for Cancer Research (AACR)
Date: 04-2009
DOI: 10.1158/0008-5472.CAN-08-2891
Abstract: Cutaneous T-cell lymphoma (CTCL) is characterized by the accumulation of malignant CD4+ T cells in the skin. Although the expression of adhesion molecules and chemokine receptors on CTCL cells has been studied extensively on ex vivo isolated cells, very little is known about the dynamics and mechanisms of CTCL trafficking in vivo. However, detailed knowledge of the molecular cues mediating CTCL migration may be used to interfere with their homing to the skin. We made use of real-time intravital epifluorescence video and two-photon microscopy to visualize malignant T cells from Sezary syndrome (SS), a leukemic variant of CTCL, in dermal microvessels in mouse ear skin. We found that SS cells rolled along dermal venules in a P-selectin– and E-selectin–dependent manner at ratios similar to CD4+ memory T cells from normal donors. We furthermore show that the chemokine CCL17/TARC, but not CCL27/CTACK, was sufficient to induce the arrest of SS cells in the microvasculature. However, a combination of both chemokines was required to induce extravasation of SS cells. Together, our experiments delineate the molecular adhesion cascade operant in SS cell homing to the skin in vivo. [Cancer Res 2009 (7):2704–8]
The methyltransferase Ezh2 controls cell adhesion and migration through direct methylation of the extranuclear regulatory protein talin
Publisher: No publisher found
DOI: 10.1038/NI.3125}
Neutrophils instruct homeostatic and pathological states in naive tissues
Publisher: Rockefeller University Press
Date: 03-10-2018
DOI: 10.1084/JEM.20181468
Abstract: Immune protection relies on the capacity of neutrophils to infiltrate challenged tissues. Naive tissues, in contrast, are believed to remain free of these cells and protected from their toxic cargo. Here, we show that neutrophils are endowed with the capacity to infiltrate multiple tissues in the steady-state, a process that follows tissue-specific dynamics. By focusing in two particular tissues, the intestine and the lungs, we find that neutrophils infiltrating the intestine are engulfed by resident macrophages, resulting in repression of Il23 transcription, reduced G-CSF in plasma, and reinforced activity of distant bone marrow niches. In contrast, diurnal accumulation of neutrophils within the pulmonary vasculature influenced circadian transcription in the lungs. Neutrophil-influenced transcripts in this organ were associated with carcinogenesis and migration. Consistently, we found that neutrophils dictated the diurnal patterns of lung invasion by melanoma cells. Homeostatic infiltration of tissues unveils a facet of neutrophil biology that supports organ function, but can also instigate pathological states.
CXCR4 identifies transitional bone marrow premonocytes that replenish the mature monocyte pool for peripheral responses
Publisher: Rockefeller University Press
Date: 10-10-2016
DOI: 10.1084/JEM.20160800
Abstract: It is well established that Ly6Chi monocytes develop from common monocyte progenitors (cMoPs) and reside in the bone marrow (BM) until they are mobilized into the circulation. In our study, we found that BM Ly6Chi monocytes are not a homogenous population, as current data would suggest. Using computational analysis approaches to interpret multidimensional datasets, we demonstrate that BM Ly6Chi monocytes consist of two distinct subpopulations (CXCR4hi and CXCR4lo subpopulations) in both mice and humans. Transcriptome studies and in vivo assays revealed functional differences between the two subpopulations. Notably, the CXCR4hi subset proliferates and is immobilized in the BM for the replenishment of functionally mature CXCR4lo monocytes. We propose that the CXCR4hi subset represents a transitional premonocyte population, and that this sequential step of maturation from cMoPs serves to maintain a stable pool of BM monocytes. Additionally, reduced CXCR4 expression on monocytes, upon their exit into the circulation, does not reflect its diminished role in monocyte biology. Specifically, CXCR4 regulates monocyte peripheral cellular activities by governing their circadian oscillations and pulmonary margination, which contributes toward lung injury and sepsis mortality. Together, our study demonstrates the multifaceted role of CXCR4 in defining BM monocyte heterogeneity and in regulating their function in peripheral tissues.
Neutrophils instruct homeostatic and pathological states in naive tissues
Publisher: No publisher found
Glycopeptide antibiotic analogs for selective inactivation and two-photon imaging of vancomycin-resistant strains
Publisher: No publisher found
DOI: 10.1039/C5CC10230H}
The impact of ischemia-reperfusion injuries on skin resident murine dendritic cells
Publisher: No publisher found
B cell-activating factor belonging to the TNF family (BAFF)-R is the principal BAFF receptor facilitating BAFF costimulation of circulating T and B cells
Publisher: No publisher found
Author Correction: Lung endothelial cell antigen cross-presentation to CD8+T cells drives malaria-associated lung injury
Publisher: Springer Science and Business Media LLC
Date: 04-11-2019
DOI: 10.1038/S41467-019-13025-4
Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Visualizing dendritic cell migration within the skin
Publisher: No publisher found
“Cloaking” on Time: A Cover-Up Act by Resident Tissue Macrophages
Publisher: Elsevier BV
Date: 04-2019
DOI: 10.1016/J.CELL.2019.03.042
Abstract: In this issue of Cell, Uderhardt et al. employed intravital two-photon microscopy to examine tissue-resident macrophage responses to sterile cellular injuries of variable size. They observed that while multi-cell "macrolesions" are characteristically pro-inflammatory, resident macrophages can "cloak" single-cell microlesions to prevent excessive neutrophil recruitment and limit subsequent tissue damage.
The BAFF/APRIL system: life beyond B lymphocytes
Publisher: Elsevier BV
Date: 05-2005
DOI: 10.1016/J.MOLIMM.2004.06.041
Abstract: B cell activating factor belonging to the TNF family (BAFF) and a proliferation-inducing ligand (APRIL) are two members of the TNF ligand superfamily. Studies of BAFF, APRIL and their receptors have highlighted the importance of this ligand/receptor system in regulating B cell homeostasis, tolerance and malignancy. Neutralizing BAFF can inhibit disease progression in animal models of autoimmunity, possibly by reducing survival of autoreactive B cells. In addition, BAFF inhibitors also prevent B lymphoma cell survival and may be useful for the treatment of lymphoid cancers. Recent work suggests that BAFF is also important for T cell activation and differentiation, an aspect that may be critical for the progression of certain autoimmune diseases. Therefore, targeting the BAFF/APRIL system may protect against autoimmunity and lymphoid cancers through the inhibition of pathogenic B and T cell functions.
Polymeric nanorods with aggregation-induced emission characteristics for enhanced cancer targeting and imaging
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C7NR09196F
Abstract: Bright polymeric AIE nanorods with higher tumor accumulation and more efficient tumor cell uptake are reported for enhanced cancer imaging.
Random migration precedes stable target cell interactions of tumor-infiltrating T cells
Publisher: Rockefeller University Press
Date: 20-11-2006
DOI: 10.1084/JEM.20060710
Abstract: The tumor microenvironment is composed of an intricate mixture of tumor and host-derived cells that engage in a continuous interplay. T cells are particularly important in this context as they may recognize tumor-associated antigens and induce tumor regression. However, the precise identity of cells targeted by tumor-infiltrating T lymphocytes (TILs) as well as the kinetics and anatomy of TIL-target cell interactions within tumors are incompletely understood. Furthermore, the spatiotemporal conditions of TIL locomotion through the tumor stroma, as a prerequisite for establishing contact with target cells, have not been analyzed. These shortcomings limit the rational design of immunotherapeutic strategies that aim to overcome tumor-immune evasion. We have used two-photon microscopy to determine, in a dynamic manner, the requirements leading to tumor regression by TILs. Key observations were that TILs migrated randomly throughout the tumor microenvironment and that, in the absence of cognate antigen, they were incapable of sustaining active migration. Furthermore, TILs in regressing tumors formed long-lasting (≥30 min), cognate antigen–dependent contacts with tumor cells. Finally, TILs physically interacted with macrophages, suggesting tumor antigen cross-presentation by these cells. Our results demonstrate that recognition of cognate antigen within tumors is a critical determinant of optimal TIL migration and target cell interactions, and argue against TIL guidance by long-range chemokine gradients.
The methyltransferase Ezh2 controls cell adhesion and migration through direct methylation of the extranuclear regulatory protein talin
Publisher: Springer Science and Business Media LLC
Date: 09-03-2015
DOI: 10.1038/NI.3125
Abstract: A cytosolic role for the histone methyltransferase Ezh2 in regulating lymphocyte activation has been suggested, but the molecular mechanisms underpinning this extranuclear function have remained unclear. Here we found that Ezh2 regulated the integrin signaling and adhesion dynamics of neutrophils and dendritic cells (DCs). Ezh2 deficiency impaired the integrin-dependent transendothelial migration of innate leukocytes and restricted disease progression in an animal model of multiple sclerosis. Direct methylation of talin, a key regulatory molecule in cell migration, by Ezh2 disrupted the binding of talin to F-actin and thereby promoted the turnover of adhesion structures. This regulatory effect was abolished by targeted disruption of the interactions of Ezh2 with the cytoskeletal-reorganization effector Vav1. Our studies reveal an unforeseen extranuclear function for Ezh2 in regulating adhesion dynamics, with implications for leukocyte migration, immune responses and potentially pathogenic processes.
Behavioural immune landscapes of inflammation
Publisher: Springer Science and Business Media LLC
Date: 05-01-2022
DOI: 10.1038/S41586-021-04263-Y
Abstract: Transcriptional and proteomic profiling of in idual cells have revolutionized interpretation of biological phenomena by providing cellular landscapes of healthy and diseased tissues
Granulopoiesis and Neutrophil Homeostasis: A Metabolic, Daily Balancing Act
Publisher: Elsevier BV
Date: 07-2019
Abstract: Granulopoiesis is part of the hematopoietic hierarchic architecture, where hematopoietic stem cells give rise to highly proliferative multipotent and lineage-committed granulocytic progenitor cells that differentiate into unipotent neutrophil progenitors. Given their short lifespan, neutrophils are rapidly cleared from circulation through specialized efferocytic macrophages. Together with an intrinsic clock, these processes contribute to circadian fluctuations, preserving self-tolerance and protection against invading pathogens. However, metabolic perturbation of granulopoiesis and neutrophil homeostasis can result in low-grade chronic inflammation, as observed with aging. During acute pathogenic infections, hematopoiesis can also be switched into emergency mode, which has been recently associated with significant neutrophil functional heterogeneity. This review focuses on a new reassessment of regulatory mechanisms governing neutrophil production, life-cycle, and ersity in health and disease.
Nanostring Analysis of Skin Biopsies from Patients with Henoch-Schonlein Purpura Reveals Genes Associated with Pathology and Heterogeneity in the Disease Process
Publisher: No publisher found
Bright AIEgen–Protein Hybrid Nanocomposite for Deep and High‐Resolution In Vivo Two‐Photon Brain Imaging
Publisher: Wiley
Date: 24-05-2019
Neutrophils contribute to inflammatory lymphangiogenesis by increasing VEGF-A bioavailability and secreting VEGF-D
Publisher: No publisher found
Deciphering human macrophage development at single-cell resolution
Publisher: Springer Science and Business Media LLC
Date: 20-05-2020
DOI: 10.1038/S41586-020-2316-7
Abstract: Macrophages are the first cells of the nascent immune system to emerge during embryonic development. In mice, embryonic macrophages infiltrate developing organs, where they differentiate symbiotically into tissue-resident macrophages (TRMs)
``Cloaking'' on Time: A Cover-Up Act by Resident Tissue Macrophages
Publisher: No publisher found
Cutaneous immunosurveillance by self-renewing dermal γδ T cells
Publisher: Rockefeller University Press
Date: 21-02-2011
DOI: 10.1084/JEM.20101824
Abstract: The presence of γδ T cell receptor (TCR)–expressing cells in the epidermis of mice, termed dendritic epidermal T cells (DETCs), is well established. Because of their strict epidermal localization, it is likely that DETCs primarily respond to epithelial stress, such as infections or the presence of transformed cells, whereas they may not participate directly in dermal immune responses. In this study, we describe a prominent population of resident dermal γδ T cells, which differ from DETCs in TCR usage, phenotype, and migratory behavior. Dermal γδ T cells are radioresistant, cycle in situ, and are partially depend on interleukin (IL)-7, but not IL-15, for their development and survival. During mycobacterial infection, dermal γδ T cells are the predominant dermal cells that produce IL-17. Absence of dermal γδ T cells is associated with decreased expansion in skin draining lymph nodes of CD4+ T cells specific for an immunodominant Mycobacterium tuberculosis epitope. Decreased CD4+ T cell expansion is related to a reduction in neutrophil recruitment to the skin and decreased BCG shuttling to draining lymph nodes. Thus, dermal γδ T cells are an important part of the resident cutaneous immunosurveillance program. Our data demonstrate functional specialization of T cells in distinct microcompartments of the skin.
Dual modal ultra-bright nanodots with aggregation-induced emission and gadolinium-chelation for vascular integrity and leakage detection
Publisher: Elsevier BV
Date: 2018
DOI: 10.1016/J.BIOMATERIALS.2017.10.031
Abstract: The study of blood brain barrier (BBB) functions is important for neurological disorder research. However, the lack of suitable tools and methods has h ered the progress of this field. Herein, we present a hybrid nanodot strategy, termed AIE-Gd dots, comprising of a fluorogen with aggregation-induced emission (AIE) characteristics as the core to provide bright and stable fluorescence for optical imaging, and gadolinium (Gd) for accurate quantification of vascular leakage via inductively-coupled plasma mass spectrometry (ICP-MS). In this report, we demonstrate that AIE-Gd dots enable direct visualization of brain vascular networks under resting condition, and that they form localized punctate aggregates and accumulate in the brain tissue during experimental cerebral malaria, indicative of hemorrhage and BBB malfunction. With its superior detection sensitivity and multimodality, we hereby propose that AIE-Gd dots can serve as a better alternative to Evans blue for visualization and quantification of changes in brain barrier functions.
A quantitative approach to histopathological dissection of elastin-related disorders using multiphoton microscopy
Publisher: No publisher found
DOI: 10.1111/BJD.12430}
Langerhans cells are precommitted to immune tolerance induction
Publisher: No publisher found
Skin‐ny deeping: Uncovering immune cell behavior and function through imaging techniques*
Publisher: Wiley
Date: 02-12-2021
DOI: 10.1111/IMR.13049
Abstract: As the largest organ of the body, the skin is a key barrier tissue with specialized structures where ongoing immune surveillance is critical for protecting the body from external insults. The innate immune system acts as first‐responders in a coordinated manner to react to injury or infections, and recent developments in intravital imaging techniques have made it possible to delineate dynamic immune cell responses in a spatiotemporal manner. We review here key studies involved in understanding neutrophil, dendritic cell and macrophage behavior in skin and further discuss how this knowledge collectively highlights the importance of interactions and cellular functions in a systems biology manner. Furthermore, we will review emerging imaging technologies such as high‐content proteomic screening, spatial transcriptomics and three‐dimensional volumetric imaging and how these techniques can be integrated to provide a systems overview of the immune system that will further our current knowledge and lead to potential exciting discoveries in the upcoming decades.
Ultrabright Organic Dots with Aggregation‐Induced Emission Characteristics for Real‐Time Two‐Photon Intravital Vasculature Imaging
Publisher: Wiley
Date: 19-08-2013
Abstract: Ultrabright organic dots with aggregation-induced emission characteristics (AIE dots) are prepared and shown to exhibit a high quantum yield, a, large two-photon absorption cross-section, and low in vivo toxicity. Real-time two-photon intravital blood vascular imaging in various tissues substantiates that the AIE dots are effective probes for in vivo vasculature imaging in a deep and high-contrast manner.
Red Emissive Biocompatible Nanoparticles from Tetraphenylethene-Decorated BODIPY Luminogens for Two-Photon Excited Fluorescence Cellular Imaging and Mouse Brain Blood Vascular Visualization
Publisher: No publisher found
Real-Time Imaging of Dendritic Cell Responses to Sterile Tissue Injury
Publisher: Elsevier BV
Date: 04-2015
DOI: 10.1038/JID.2014.506
B Cell-Activating Factor Belonging to the TNF Family Acts through Separate Receptors to Support B Cell Survival and T Cell-Independent Antibody Formation
Publisher: The American Association of Immunologists
Date: 15-08-2004
DOI: 10.4049/JIMMUNOL.173.4.2331
Abstract: The TNF-related ligand, B cell-activating factor belonging to the TNF family (BAFF), is necessary for normal B cell development and survival, and specifically binds the receptors transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI), B cell maturation Ag (BCMA), and BAFF-R. Similarities between mice completely lacking BAFF and A/WySnJ strain mice that express a naturally occurring mutant form of BAFF-R suggest that BAFF acts primarily through BAFF-R. However, the nearly full-length BAFF-R protein expressed by A/WySnJ mice makes unambiguous interpretation of receptor function in these animals impossible. Using homologous recombination we created mice completely lacking BAFF-R and compared them directly to A/WySnJ mice and to mice lacking BAFF. BAFF-R-null mice exhibit loss of mature B cells similar to that observed in BAFF−/− and A/WySnJ mice. Also, mice lacking both TACI and BCMA simultaneously exhibit no B cell loss, thus confirming that BAFF-R is the primary receptor for transmitting the BAFF-dependent B cell survival signal. However, while BAFF-R-null mice cannot carry out T cell-dependent Ab formation, they differ from BAFF-deficient mice in generating normal levels of Ab to at least some T cell-independent Ags. These studies clearly demonstrate that BAFF regulates Ab responses in vivo through receptors in addition to BAFF-R.
Plasmodium vivax: restricted tropism and rapid remodeling of CD71-positive reticulocytes
Publisher: American Society of Hematology
Date: 19-02-2015
DOI: 10.1182/BLOOD-2014-08-596015
Abstract: Plasmodium vivax merozoites preferentially infect a subgroup of reticulocytes generally restricted to the bone marrow. Accelerated “maturation” of infected reticulocytes.
Migratory Dermal Dendritic Cells Act as Rapid Sensors of Protozoan Parasites
Publisher: No publisher found
In vivo label-free functional photoacoustic monitoring of ischemic reperfusion
Publisher: No publisher found
Silole-Based Red Fluorescent Organic Dots for Bright Two-Photon Fluorescence in vitro Cell and in vivo Blood Vessel Imaging
Publisher: Wiley
Date: 23-12-2016
Streamlining volumetric multi-channel image cytometry using hue-saturation-brightness-based surface creation
Publisher: No publisher found
Polymeric nanorods with aggregation-induced emission characteristics for enhanced cancer targeting and imaging
Publisher: No publisher found
DOI: 10.1039/C7NR09196F}
Polymerization-Enhanced Two-Photon Photosensitization for Precise Photodynamic Therapy
Publisher: No publisher found
3-Dimensional Optical Clearing and Imaging of Pruritic Atopic Dermatitis and Psoriasis Skin Reveals Downregulation of Epidermal Innervation
Publisher: Elsevier BV
Date: 05-2019
Dynamic Imaging of CD8(+) T Cells and Dendritic Cells during Infection with Toxoplasma gondii
Publisher: No publisher found
Visualizing dendritic cell migration within the skin
Publisher: Springer Science and Business Media LLC
Date: 06-11-2008
DOI: 10.1007/S00418-008-0531-7
Abstract: Dendritic cells (DCs) within the skin are a heterogeneous population of cells, including Langerhans cells of the epidermis and at least three subsets of dermal DCs. Collectively, these DCs play important roles in the initiation of adaptive immune responses following antigen challenge of the skin as well as being mediators of tolerance to self-antigen. A key functional aspect of cutaneous DCs is their migration both within the skin and into lymphatic vessels, resulting in their emigration to draining lymph nodes. Here, we discuss our current understanding of the requirements for successful DC migration in and from the skin, and introduce some of the microscopic techniques developed in our laboratory to facilitate a better understanding of this process. In particular, we detail our current use of multi-photon excitation (MPE) microscopy of murine skin to dissect the migratory behavior of DCs in vivo.
Capturing the Fantastic Voyage of Monocytes Through Time and Space
Publisher: Frontiers Media SA
Date: 16-04-2019
Illuminating the covert mission of mononuclear phagocytes in their regional niches.
Publisher: Elsevier BV
Date: 02-2017
DOI: 10.1016/J.COI.2017.12.004
Abstract: Monocytes, dendritic cells (DCs) and macrophages have been classically categorized into the mononuclear phagocyte system (MPS) based on their similar functional and phenotypic characteristics. While an increasing amount of research has revealed substantial ontogenic and functional differences among these cells, the reasons behind their heterogeneity and strategic positioning in specific niches throughout the body are yet to be fully elucidated. In this review, we outline how recent advances in intravital imaging studies have dissected this phenomenon and have allowed us to appreciate how MPS cells exploit their regional niches to specialize and maximize their functional properties. Understanding their cellular behavior in each of their specialized microenvironment will eventually allow us to target specific cells and their behavioral patterns for improved vaccine and therapeutic purposes.
Heterogeneity of neutrophils
Publisher: Springer Science and Business Media LLC
Date: 28-02-2019
DOI: 10.1038/S41577-019-0141-8
Abstract: Structured models of ontogenic, phenotypic and functional ersity have been instrumental for a renewed understanding of the biology of immune cells, such as macrophages and lymphoid cells. However, there are no established models that can be used to define the ersity of neutrophils, the most abundant myeloid cells. This lack of an established model is largely due to the uniquely short lives of neutrophils, a consequence of their inability to ide once terminally differentiated, which has been perceived as a roadblock to functional ersity. This perception is rapidly evolving as multiple phenotypic and functional variants of neutrophils have been found, both in homeostatic and disease conditions. In this Opinion article, we present an overview of neutrophil heterogeneity and discuss possible mechanisms of ersification, including genomic regulation. We suggest that neutrophil heterogeneity is an important feature of immune pathophysiology, such that co-option of the mechanisms of ersification by cancer or other disorders contributes to disease progression.
Fate Mapping Analysis Reveals That Adult Microglia Derive from Primitive Macrophages
Publisher: American Association for the Advancement of Science (AAAS)
Date: 05-11-2010
Abstract: Microglia are the resident macrophages of the central nervous system and are associated with neurodegeneration and brain inflammatory diseases. Although the developmental origins of other tissue macrophage populations are well established, the origins of microglia remain controversial. Ginhoux et al. (p. 841 , published online 21 October) used in vivo lineage tracing studies to show that microglia arise early in mouse development and derive from primitive macrophages in the yolk sac. This is in contrast to other cells of the mononuclear phagocyte system, which arise later in development from a distinct progenitor population.
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