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UPCOMING SEMINAR - Dr Kirsten Ward-Hartstonge

Posted by Jennifer van Eunen on 13 March 2023 | Comments

1:00pm, Monday, 13 March
Room BIG13, Ground Floor
Biochemistry Building
710 Cumberland St


Dr Kirsten Ward-Hartstonge

University of Otago, Microbiology & Immunology

‘Differential expression of integrin β1 and β7 defines functionally distinct human CD4+ T cell subsets in health and inflammatory bowel disease’

Inflammatory bowel disease (IBD; Crohn’s disease and ulcerative colitis), is a chronic inflammatory group of disorders of the gastrointestinal tract that affects about 7 million people worldwide.  Anti-integrin therapy to block β7 or β1 integrins on immune cells is a treatment aimed to inhibit the trafficking of inflammatory T cells to the gut in people with IBD.  There are currently multiple anti-integrin therapies in clinical trials that target different combinations of integrins. However, it is unclear if either β1+ or β7+ T cells are inflammatory, if integrin expression on T cells is modified in people with IBD, and how the balance of integrin expression is controlled. We compared the integrin expression and T cell function from the gut of healthy donors and people with IBD and found there was a shift from β7+ to β1+ Τ cells in people with IBD, and that β1+ Τ cells displayed a pathogenic phenotype in those with IBD.  We found that β1+andβ7+T cells from the blood and gut produced unique cytokines and had distinct metabolic signatures, even after in vitro culturing, indicating that they are stable T cell populations.  Using CRISPR-mediated PTEN knockout and drugs to modify p-AKT473, we showed that integrin expression can be modified by mTORC2 activity.

Overall, we found that differential integrin expression may identify functionally and metabolically distinct subsets of human T cells that are associated with inflammation in people with IBD.  This work indicates that mTORC2 may be a potential therapeutic target to modify the balance of pathogenic cells in the gut of people with IBD.