Intestinal type 1 regulatory T cells migrate to periphery to suppress diabetogenic T cells and prevent diabetes development

Significance Past and current treatments for type 1 diabetes (T1D) have all suffered from adverse effects due to severe immune suppression or a lack of efficacy. A better understanding of the mechanisms and limitations of these therapies may help to maximize patient responses to treatment or elicit new ideas for a cure. Here, we discover a role for intestinal type 1 regulatory T (Tr1) cells in preventing autoimmune diabetes and provide mechanistic insight to explain the better efficacy of combination therapy in disease treatment. Our results also highlight the influence of dysbiotic gut microbiota on promotion of intestinal Tr1 cells and suggest that strategies targeting mucosal tissue to induce Tr1 in vivo might be used as a therapeutic approach for T1D.