Type 1 diabetes (T1D) results from autoimmune attack of the insulin-producing beta cells, and consequently glucose can no longer be absorbed and utilized by the body. Although patients receive insulin injections to help regulate blood glucose, the regulation achieved is far from ideal and patients develop long-term complications. Current strategies to prevent T1D involve developing immunomodulatory therapies to arrest or slow disease progression of the autoimmune process. It is likely such immunomodulatory therapies will have an increased chance of success if delivered prior to the development of autoimmunity. Therefore, understanding the genetic basis of T1D is very important to the identification of ‘at risk’ individuals prior to the onset an autoimmune response to their islets so that preventative immunotherapies can be developed. MIELT1D aims to understand the role of ß2M/MHC class I in susceptibility to T1D. In particular, MIELT1D aims to understand the selection of diabetogenic CD8 T cell by the ß2M/MHCclass I expression level during thymic development, in order to develop markers for targeting these cells in predisposed individuals. Secondly we propose to test the peripheral blood of patients with T1D to determine whether ß2M expression level is correlated with susceptibility to disease, and whether there are polymorphisms within the promoter of the ß2M gene that may be used as a genetic screen for T1D risk. The multidisciplinary interaction of leading international expertise in the pathology of diabetes and autoimmunity, the Immunology of T cell development in the thymus, and state-of-the-art genetic screening platforms, along with an interdisciplinary approach using inbred diabetes prone animals to probe important molecular questions not possible to address in humans due to the complex genetics, are essential to achieve these aims. MIELT1D will lead to the design of early therapeutical intervention so as to lowering the burden of T1D in Europe.
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