Treg insufficiency in autoimmune diabetes is driven by selective loss of Neuropilin-1 on intra-islet regulatory T cells

Strategies targeting Treg insufficiency are vital for treating autoimmune diseases like T1D. Our findings highlight the critical role of Neuropilin 1 (Nrp1) in stabilizing Tregs within pancreatic islets. Boosting Nrp1 levels delays diabetes onset by enhancing Treg function. This underscores Nrp1 as a potential target for bolstering Treg activity and combating autoimmune diseases. Our experimental design aimed to explore the influence of Neuropilin 1 (Nrp1) expression on regulatory T cell (Treg) function within NOD mouse islets, a model of autoimmune diabetes. We first identified Tregs lacking Nrp1 expression and observed diminished function. Augmenting Nrp1 levels delayed disease onset, suggesting its importance in Treg function and stability. Comparing Nrp1-induced Tregs to wild-type counterparts, we conducted single-cell RNA sequencing (scRNAseq) experiments to elucidate transcriptional changes. Our findings revealed improved Treg activity in response to Nrp1 expression within the islets, indicating potential therapeutic implications for autoimmune diseases.