Type 1 Diabetes Clinical Trial
Official title:
Immune Function and the Progression to Type 1 Diabetes:
To elucidate the mechanisms by which type 1 diabetes-associated genes; IFIH1, TYK2, IKZF4, as well as total genetic risk, impart functional immunoregulatory abnormalities that result in expansion of self-reactive adaptive immune cells, defective regulatory/effector mechanisms in T cells, inflammatory antigen presenting cells, and abnormal immune function in T cells and B cells.
Newly proposed studies will identify the inflammatory cues that draw immune cells into islets for disease initiation (Project 1); probe the motility of immune cells through inflamed vasculature to the target organ and antigen priming sites within secondary lymphatics (Project 2); and characterize the T1D-associated adaptive immune signatures in blood and immune tissues (Project 3). The overall hypothesis of the renewed P01 states: 1) the impact of T1D-risk variants will vary by tissue, cell subset, and activation state, and 2) risk variants, cellular stress, and defects in immunologic pathways are key to engender the autoimmune destruction of pancreatic B-cells that results in T1D. ;
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