Identifying antigen-presenters in the islets during type 1 diabetes 3721

Abstract Description Type 1 diabetes (T1D) is an autoimmune disorder where islet antigen-specific T cells destroy insulin-producing beta cells. While the role of T cells in T1D is well understood, the contribution of myeloid cells remains less clear. Our analyses show that macrophages are the primary immune cell population in human islets, with most islet T cells directly contacting myeloid cells. T cell-myeloid cell contacts are further increased in islets from T1D donors. Single-cell RNA sequencing reveals that in early T1D, islet macrophages exhibit a transcriptional decrease in antigen processing and presentation. In NOD mice, antigen-dependent T cell-myeloid cell interactions decrease as insulitis progresses, suggesting a shift in the T cell response that may impact disease progression. We hypothesize that macrophages are the primary antigen-presenting cells in early T1D that restimulate autoreactive T cells. Using the LIPSTIC method, we tracked antigen-specific T cells-myeloid cells interactions in NOD mice and found that macrophages, rather than dendritic cells, are the dominant antigen-presenting subset within islets. Depleting macrophages significantly reduced sustained T cell-myeloid interactions, highlighting their role in T cell restimulation. These results suggest that targeting islet macrophages could offer a promising therapeutic strategy. Our research aims to identify specific myeloid subsets involved in T1D progression and explore approaches to restore islet homeostasis. Funding Sources NIH R01DK111733 Topic Categories Basic Autoimmunity (BA)