ORCID Profile
0000-0002-9618-3088
Current Organisation
Monash University
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Publisher: Springer International Publishing
Date: 2016
Publisher: Informa UK Limited
Date: 07-05-2015
Publisher: Wiley
Date: 03-2016
DOI: 10.1038/CTI.2016.6
Publisher: Oxford University Press (OUP)
Date: 13-04-2012
DOI: 10.1093/NAR/GKS319
Publisher: Cold Spring Harbor Laboratory
Date: 15-04-2021
DOI: 10.1101/2021.04.15.439921
Abstract: MARCH1 and MARCH8 are ubiquitin ligases that control the expression and trafficking of critical immunoreceptors. Understanding of their function is h ered by three major knowledge gaps: (i) it is unclear which cell types utilize these ligases (ii) their level of redundancy is unknown and (iii) most of their putative substrates have been described in cell lines, often overexpressing MARCH1 or MARCH8, and it is unclear which substrates are regulated by either ligase in vivo . Here we address these questions by systematically analyzing the immune cell repertoire of MARCH1- or MARCH8-deficient mice, and applying unbiased proteomic profiling of the plasma membrane of primary cells to identify MARCH1 and MARCH8 substrates. Only CD86 and MHC II were unequivocally identified as immunoreceptors regulated by MARCH1 and MARCH8, but each ligase carried out its function in different tissues. MARCH1 regulated MHC II and CD86 in professional and “atypical” antigen presenting cells of hematopoietic origin, whereas MARCH8 only operated in non-hematopoietic cells. Our results reveal that the range of cells constitutively endowed with antigen-presentation capacity is wider than generally appreciated. They also establish MARCH1 and MARCH8 as specialized regulators of CD4+ T cell immunity in two ontogenically distinct cellular compartments.
Publisher: Elsevier BV
Date: 2017
DOI: 10.1016/J.MOLIMM.2016.12.010
Abstract: Targeting antigen (Ag) to dendritic cell (DC) surface receptors is a potential new mode of vaccination. C-type lectin-like receptors Clec9A and Clec12A are attractive receptor targets however their targeting in vivo elicits significantly different outcomes for unknown reasons. To gain insight into the mechanisms responsible, we have examined the intrinsic capacity of Clec9A and Clec12A to elicit MHC I and MHC II Ag presentation following ex vivo targeting with primary murine DC. Both receptors exhibited high rates of internalization by CD8
Publisher: Informa UK Limited
Date: 05-12-2013
DOI: 10.4161/AUTO.26448
Abstract: HSPA8/HSC70 protein is a fascinating chaperone protein. It represents a constitutively expressed, cognate protein of the HSP70 family, which is central in many cellular processes. In particular, its regulatory role in autophagy is decisive. We focused this review on HSC70 structure-function considerations and based on this, we put a particular emphasis on HSC70 targeting by small molecules and peptides in order to develop intervention strategies that deviate some of HSC70 properties for therapeutic purposes. Generating active biomolecules regulating autophagy via its effect on HSC70 can effectively be designed only if we understand the fine relationships between HSC70 structure and functions.
Publisher: Informa UK Limited
Date: 26-02-2015
Publisher: Elsevier BV
Date: 06-2015
DOI: 10.1016/J.COI.2014.12.006
Abstract: Processing and loading of antigen into major histocompatibility complex molecules (MHC) occurs in specific intracellular compartments. Accessing MHC loading compartments requires trafficking via specific pathways, some of which have yet to be fully characterized. For MHC I, cross-presentation involves antigen trafficking to a specialised compartment. We review the features of this compartment and how it is accessed by different mechanisms of antigen capture and internalization. We also summarize advances in understanding how antigen efficiently accesses the MHC II loading compartment, with particular focus on the role of autophagy. Understanding the mechanisms that control how antigen is trafficked to specific compartments for loading and presentation is crucial if these pathways are to be manipulated more effectively in settings of vaccination.
Publisher: Elsevier BV
Date: 12-2018
DOI: 10.1016/J.SEMCDB.2017.12.009
Abstract: Dendritic cells (DC) are professional antigen presenting cells comprising a variety of subsets, as either resident or migrating cells, in lymphoid and non-lymphoid organs. In the steady state DC continually process and present antigens on MHCI and MHCII, processes that are highly upregulated upon activation. By expressing differential sets of pattern recognition receptors different DC subsets are able to respond to a range of pathogenic and danger stimuli, enabling functional specialisation of the DC. The knowledge of functional specialisation of DC subsets is key to efficient priming of T cells, to the design of effective vaccine adjuvants and to understanding the role of different DC in health and disease. This review outlines mouse and human steady state DC subsets and key attributes that define their distinct functions.
Publisher: Elsevier BV
Date: 08-2014
DOI: 10.1016/J.BIOMATERIALS.2014.05.017
Abstract: Dendrons constituted of an adamantane core, a focal point and three arms, were synthetized starting from a multifunctional adamantane derivative. Maleimido groups at the periphery of the scaffold were used to covalently attach the peptide called P140, a therapeutic phosphopeptide controlling disease activity in systemic lupus, both in mice and patients. Biotinylation of the trimers at the focal point was performed using click chemistry and the conjugates were studied in terms of solubility, binding affinity to its receptor, the HSPA8/HSC70 chaperone protein, effect on HSPA8 folding property and in vivo activity. The results showed that the trimerization of P140 peptide does not trigger aggregation or steric hindrances during the interaction with HSPA8 protein. Compared to the monomeric cognate peptide, the trivalent P140 peptide displayed the same capacity, in vitro, to down-regulate HSPA8 activity and, in vivo in MRL/lpr lupus-prone mice, to reduce abnormal blood hypercellularity. The control trimer synthesized with the same scaffold and a scrambled sequence of P140 showed no effect in vivo. This work reveals that adamantane-based scaffolds with a well-defined spatial conformation are promising trivalent systems for molecular recognition and for biomedical applications.
Publisher: The American Association of Immunologists
Date: 11-2021
Abstract: MHC class II (MHC II) Ag presentation by dendritic cells (DCs) is critical for CD4+ T cell immunity. Cell surface levels of MHC II loaded with peptide is controlled by ubiquitination. In this study, we have examined how MHC II ubiquitination impacts immunity using MHC IIKRKI/KI mice expressing mutant MHC II molecules that are unable to be ubiquitinated. Numbers of conventional DC (cDC) 1, cDC2 and plasmacytoid DCs were significantly reduced in MHC IIKRKI/KI spleen, with the remaining MHC IIKRKI/KI DCs expressing an altered surface phenotype. Whereas Ag uptake, endosomal pH, and cathepsin protease activity were unaltered, MHC IIKRKI/KI cDC1 produced increased inflammatory cytokines and possessed defects in Ag proteolysis. Immunization of MHC IIKRKI/KI mice identified impairments in MHC II and MHC class I presentation of soluble, cell-associated and/or DC-targeted OVA via mAb specific for DC surface receptor Clec9A (anti-Clec9A-OVA mAb). Reduced T cell responses and impaired CTL killing was observed in MHC IIKRKI/KI mice following immunization with cell-associated and anti-Clec9A-OVA. Immunization of MHC IIKRKI/KI mice failed to elicit follicular Th cell responses and generated barely detectable Ab to anti-Clec9A mAb-targeted Ag. In summary, MHC II ubiquitination in DCs impacts the homeostasis, phenotype, cytokine production, and Ag proteolysis by DCs with consequences for Ag presentation and T cell and Ab-mediated immunity.
Publisher: Elsevier BV
Date: 09-2012
DOI: 10.1016/J.JAUT.2012.05.016
Abstract: After a long period where the potential of therapeutic peptides was let into oblivion and even dismissed, there is a revival of interest in peptides as potential drug candidates. Novel strategies for limiting metabolism and improve their bioavailability, and alternative routes of administration have emerged. This resulted in a large number of peptide-based drugs that are now being marketed in different indications. Regarding autoimmunity, successful data have been reported in numerous mouse models of autoimmune inflammation, yet relatively few clinical trials based on synthetic peptides are currently underway. This review reports on peptides that show much promises in appropriate mouse models of autoimmunity and describes in more detail clinical trials based on peptides for treating autoimmune patients. A particular emphasis is given to the 21-mer peptide P140/Lupuzor that has completed successfully phase I, phase IIa and phase IIb clinical trials for systemic lupus erythematosus.
Location: Australia
No related grants have been discovered for Christophe Macri.