Polysaccharide Metabolism in the Infant Gut: Pathways to Immune Homeostasis
In-person only
We identify a host-microbiome interaction fundamental to the aetiology of Type 1 diabetes (T1D), a T-cell-mediated destruction of pancreatic β cells, owing to a loss of immune tolerance to primary insulin epitope. We show how variation in the human leukocyte antigen (HLA) class II region, DQβ57, the strongest T1D genetic risk factor, induces a thymic selection bias that favors increased frequency of insulin reactive T cells in the periphery. Furthermore, we describe a large set of gut commensal proteins, enriched with enzymes involved in metabolism of polysaccharides, with similarity to the primary insulin epitope. We demonstrate that islet infiltrates from early stage T1D contain T cells cross-reactive to bacterial mimics and insulin peptides. Our findings establish a connection between microbial metabolism of polysaccharides, dysbiosis in the infant gut, and antigen-specific immune responses to insulin, offering new strategies for disease prevention.
Date:
6 June 2024, 10:00
Venue:
Kennedy Institute of Rheumatology, Headington OX3 7FY
Venue Details:
Lecture Theatre
Speaker:
Dr Marcin Pekalski (University of Oxford)
Organising department:
Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS)
Organiser:
Doris Chan (Kennedy Institute of Rheumatology)
Organiser contact email address:
doris.chan@kennedy.ox.ac.uk
Host:
Dr Jethro Johnson (The Kennedy Institute of Rheumatology)
Part of:
Kennedy Institute Seminars
Booking required?:
Not required
Audience:
Members of the University only
Editor:
Doris Chan
