University of California, San Francisco (UCSF)

Next Generation Analysis of Type 1 Diabetes

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The development of T1D represents the result of a failure of immune tolerance to insulin-producing ? cells. Despite advances in insulin therapy and subsequent glucose control, patients are required to inject insulin daily throughout their lives, regulate their diet and blood sugar levels, and deal with life-long uncertainties about end-organ complications. Current efforts to modulate disease activity have largely relied on antigen-specific and antigen non-specific immunomodulatory therapies. None of these has achieved immune tolerance or resulted in long-term insulin independence. Antigen-specific tolerogenic therapies are appealing from a safety point-of-view since they are not expected to induce global immunosuppression like systemic approaches. This has led to intensive efforts by many groups to define self-antigens recognized by effector T cells that drive disease in T1D patients.

Our Network brings together basic and translational researchers who are committed to the development and enablement of immune tolerance-based therapeutics in T1D. Our work begins to unravel exactly how the thymic and peripheral expression of self-antigens like insulin impact the selection and expansion of autoreactive Treg cells. What drives self-antigen recognition by Tregs that are generated both in the thymus and the periphery.  We will assess genes that a crucial in Treg stability in T1D.  Our proposed research will have a major impact on our understanding of how immune tolerance is controlled and potentially lead to novel antigens-specific Treg-based immunotherapy strategies in T1D.  In addition, we will be performing a deeper characterization of the key cell populations involved in the pathogenesis of T1D.