"The development of TID relies on interrelationships between cells of the immune system (e.g., DC, Teff, Treg), genes imparting susceptibility or resistance to the disease, and certain cytokines that appear key to the process underlying the autoimmune destruction of insulin producing pancreatic p cells." Variations on such a statement are common to most descriptions of TID to the point of serving as a central dogma for the pathogenesis of this disorder. While a broad body of evidence certainly exists to support this notion (and we ourselves believe it true), the exact mechanisms by which autoimmune (3 cell destruction is facilitated remain unclear. In addition, the relative contributions of each facet (i.e., cells, genes, cytokines) to the process remain, to a large extent, unknown. This forms a major void for attempts seeking to prevent and/or reverse the disease, as well as to identify improved biomarkers of disease progression &therapeutic efficacy. For these reasons, we deem it essential to perform the proposed research . Within this Specific Aims section of the POI overview, we identify our overall goals as well as the expected mechanistic / experimental outcomes.

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