Type 1 diabetes (T1D) is driven by the irregular immune reaction attacking the insulin producing beta-cells. By understanding the detailed mechanisms by which the abnormal immune system function, the therapeutic intervention can be developed to target specific compartments driving T1D and leave immune system intact to routine infections. One type of immune cells, T helper (Th) cells functions by recruiting and activating other immune populations to clear pathogens as well as drive T1D progression. Scientists have identified two surface receptors, TIGIT and CD226, associated with Th cell function; however, the regulation and detailed mechanisms have not been addressed. Therefore, we focus on elucidating their roles in Th cells during T1D. Dr. Yeh proposes to assess TIGIT and CD226 function by directly modifying their expression levels in Th cells followed by examining immune function. In addition, the critical question as if the defects of these receptors cause the misguided immune reaction will be defined by analyzing T1D and healthy human peripheral blood samples and tissue samples through nPOD (Networks for Pancreatic Organ Donors with Diabetes) program. Comparing immune compartments in inflammatory tissues will allow scientists to thoroughly understand the roles of both receptors during disease. Overall, by extensively understanding how these receptors contribute to immune cell function during T1D will provide a tremendous outcome for safe-yet-effective therapies.