• Le 29 septembre 2020
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  • 16h via Zoom

“Human CD4+ T cells in Gut Infection and Inflammation: Potential Diagnostic and Therapeutic Applications"

Dr Laura COOK,
PhD Senior Research Officer, The University of Melbourne, Melbourne, Australia

Abstract : While effector CD4+ T cells are important in driving immunity towards gut pathogens, regulatory T cells (Tregs) are critical for maintaining gut homeostasis. Clostridium difficile infection (CDI) is a leading cause of infectious diarrhea, and the Centers for Disease Control and Prevention has listed C. difficile as an urgent threat to antimicrobial resistance. We identified that CD4+ T cell responses to the C. difficile secreted toxin B are a marker of patients with active CDI. Reduced Th17 proportions within these cells was associated with severe, recurrent CDI and was also a feature of inflammatory bowel disease (IBD) patients with no history of CDI. This suggests modulation of IL17/Th17 cells as a potential therapeutic approach to treat CDI; and that undiagnosed CDI may be contributing to dysbiosis and symptoms in IBD patients. In addition to eliminating underlying infectious disease, an effective IBD treatment strategy needs to suppress destructive innate and adaptive immune responses and support gut health. We compared the ability of two Treg subsets to exert these effects to identify the ideal cell therapy candidate. Compared to FOXP3+ regulatory T cells, IL10-producing type 1 regulatory T (Tr1) cells had unique functions, including IL10-mediated suppression of inflammation and IL22-mediated epithelial barrier protection. Therefore, Tr1 cells may be a better candidate for treatment of such chronic inflammatory intestinal diseases. Bio: Dr Laura Cook is a human immunologist, whose research focuses on the role of CD4+ T cells, particularly regulatory T cells, in infectious and autoimmune diseases. Dr Cook completed her PhD at the Kirby Institute, University of New South Wales, Sydney, Australia in 2014 where she developed an assay to isolate humanantigen-specific CD39+ regulatory T cells (Tregs) and identified that, in coeliac disease patients, gluten-specific CD39+ Tregs have a functional defect that may contribute to disease. Dr Cook completed 6 years postdoctoral research at The University of British Columbia, Vancouver, Canada with Dr Megan Levings, a world-expert in human Tregs, and Dr Ted Steiner, an infectious diseases specialist. Dr Cook’s postdoctoral research focused on the therapeutic potential of human regulatory T cell subsets and characterising CD4+ T cell responses to bacterial flagellin (in inflammatory bowel disease), insulin antigens (in Type 1 diabetes) and C. difficile toxins (during infection). Dr Cook is interested in pursuing functional studies of antigen-specific T cells in infectious disease, in particular identifying the role of regulatory T cells in the development of immune memory.

Invitée par le Pr Antoine Roquilly