ORCID Profile
0000-0003-2115-5389
Current Organisation
University of Würzburg
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Publisher: Elsevier BV
Date: 04-2022
DOI: 10.1016/J.IMMUNI.2022.03.006
Abstract: Reinvigoration of exhausted CD8
Publisher: SAGE Publications
Date: 20-01-2010
Abstract: Nogo-A is an oligodendroglial neurite outgrowth inhibitor, the deactivation of which enhances brain plasticity and functional recovery in animal models of stroke. Nogo-A's role in the reperfused brain tissue was still unknown. By using Nogo-A −/− mice and mice in which Nogo-A was blocked with a neutralizing antibody (11C7) that was infused into the lateral ventricle or striatum, we show that Nogo-A inhibition goes along with decreased neuronal survival and more protracted neurologic recovery, when deactivation is constitutive or induced 24 h before, but not after focal cerebral ischemia. We show that in the presence of Nogo-A, RhoA is activated and Rac1 and RhoB are deactivated, maintaining stress kinases p38/MAPK, SAPK/JNK1/2 and phosphatase-and-tensin homolog (PTEN) activities low. Nogo-A blockade leads to RhoA deactivation, thus overactivating Rac1 and RhoB, the former of which activates p38/MAPK and SAPK/JNK1/2 via direct interaction. RhoA and its effector Rho-associated coiled-coil protein kinase2 deactivation in turn stimulates PTEN, thus inhibiting Akt and ERK1/2, and initiating p53-dependent cell death. Our data suggest a novel role of Nogo-A in promoting neuronal survival by controlling Rac1/RhoA balance. Clinical trials should be aware of injurious effects of axonal growth-promoting therapies. Thus, Nogo-A antibodies should not be used in the very acute stroke phase.
Publisher: Springer Science and Business Media LLC
Date: 05-09-2014
DOI: 10.1038/NCOMMS5821
Abstract: Effector and memory CD4(+) T cells acquire distinct migratory properties depending on the type and location of the immune responses. Due to the highly dynamic nature of T cell circulation, the comprehensive analysis of these migratory routes requires dedicated experimental approaches. Here, we analyse the migration of effector/memory CD4(+) T cells by long-term in vivo cell tracking. We identify a resident population of antigen-experienced CD4(+) T cells that resides in lymph nodes and Peyer's patches without circulation or proliferation. Resident CD4(+) T cells constitute up to 50% of all effector/memory cells, including, but not limited to, follicular helper T cells. Furthermore, these non-circulating T cells possess a distinct T cell receptor repertoire and accumulate in Peyer's patches after continuous oral antigen exposure. Our results provide the first direct evidence for a resident population of effector/memory CD4(+) T cells that is retained in lymphoid tissues.
Publisher: Elsevier BV
Date: 07-2014
DOI: 10.1038/MI.2013.105
Publisher: Wiley
Date: 11-04-2019
DOI: 10.1111/IMR.12753
Abstract: The initiation of T lymphocyte responses within secondary lymphoid organs involves interactions with different subsets of dendritic cells (DCs). Recent studies have revealed the complexity of microanatomical organization within lymphoid organs. Exactly how T cells and DCs locate each other and the type of cellular interactions required for optimal priming of effector and memory T cell responses are beginning to be unraveled. Here we review advances in our understanding of how T cell priming is choreographed during infections, highlight the importance of cell positioning in this process and discuss how a spectrum of cellular interactions shapes T cell activation and differentiation.
Publisher: Tsinghua University Press
Date: 05-11-2012
Publisher: Elsevier BV
Date: 08-2023
Publisher: Springer Science and Business Media LLC
Date: 29-06-2015
DOI: 10.1038/NI.3213
Abstract: Secretory immunoglobulin A (SIgA) shields the gut epithelium from luminal antigens and contributes to host-microbe symbiosis. However, how antibody responses are regulated to achieve sustained host-microbe interactions is unknown. We found that mice and humans exhibited longitudinal persistence of clonally related B cells in the IgA repertoire despite major changes in the microbiota during antibiotic treatment or infection. Memory B cells recirculated between inductive compartments and were clonally related to plasma cells in gut and mammary glands. Our findings suggest that continuous ersification of memory B cells constitutes a central process for establishing symbiotic host-microbe interactions and offer an explanation of how maternal antibodies are optimized throughout life to protect the newborn.
Publisher: Elsevier BV
Date: 11-2010
DOI: 10.1016/J.RBMO.2010.05.022
Abstract: This study aimed to demonstrate the presence of erythropoietin (EPO) receptor on spermatozoa. Whole ejaculates of four healthy volunteers were incubated with polyclonal rabbit anti-EPO receptor and subsequently stained with a Cy-3 labelled secondary antibody. Four slides per subject were analysed, no staining was observed in slides incubated with either primary or secondary antibody alone. EPO receptor staining was positive in 92±8% of EPO pre-treated and 91±4% of non-treated sperm cells. The results suggest that spermatozoa express EPO receptor on plasma membrane, which might act to protect these cells from damage after ejaculation.
Publisher: Elsevier BV
Date: 10-2022
DOI: 10.1016/J.IMMUNI.2022.07.019
Abstract: Lymphatic transport of molecules and migration of myeloid cells to lymph nodes (LNs) continuously inform lymphocytes on changes in drained tissues. Here, using LN transplantation, single-cell RNA-seq, spectral flow cytometry, and a transgenic mouse model for photolabeling, we showed that tissue-derived unconventional T cells (UTCs) migrate via the lymphatic route to locally draining LNs. As each tissue harbored a distinct spectrum of UTCs with locally adapted differentiation states and distinct T cell receptor repertoires, every draining LN was thus populated by a distinctive tissue-determined mix of these lymphocytes. By making use of single UTC lineage-deficient mouse models, we found that UTCs functionally cooperated in interconnected units and generated and shaped characteristic innate and adaptive immune responses that differed between LNs that drained distinct tissues. Lymphatic migration of UTCs is, therefore, a key determinant of site-specific immunity initiated in distinct LNs with potential implications for vaccination strategies and immunotherapeutic approaches.
Publisher: Springer Science and Business Media LLC
Date: 12-06-2018
DOI: 10.1038/S41598-018-27339-8
Abstract: During immune responses, T cells differentiate into subsets with different functions and migratory properties. Here we characterize migratory behavior of endogenous αβ CD8 + and γδ T cells in lymph nodes by long-term tracking following in vivo photoconversion. We identified subsets of γδ T cells with distinct circulation kinetics that closely mirrored migratory subsets of αβ CD8 + T cells. Notably, αβ CD8 + and γδ T cells both comprised resident populations which stayed in lymph nodes for 4 weeks without circulation or proliferation. Furthermore, in contrast to the common conception, we observed that central memory αβ CD8 + T cells circulate with slower kinetics than naïve cells. Our results show that, similar to αβ T cells, γδ T cells can acquire distinct migratory properties during their development and differentiation and reveal unexpected intricacies of T cell migratory patterns.
Publisher: Wiley
Date: 14-09-2011
Publisher: American Association for the Advancement of Science (AAAS)
Date: 24-10-2023
No related grants have been discovered for Milas Ugur.