A Minor Subset of Batf3-Dependent Antigen-Presenting Cells in Islets of Langerhans Is Essential for the Development of Autoimmune Diabetes

Autoimmune diabetes is characterized by inflammatory infiltration; however, the initiating events are poorly understood. We found that the islets of Langerhans in young nonobese diabetic (NOD) mice contained two antigen-presenting cell (APC) populations: a major macrophage and a minor CD103+ dendritic cell (DC) population. By 4 weeks of age, CD4+ T cells entered islets coincident with an increase in CD103+ DCs. In order to examine the role of the CD103+ DCs in diabetes, we examined Batf3-deficient NOD mice that lacked the CD103+ DCs in islets and pancreatic lymph nodes. This led to a lack of autoreactive T cells in islets and, importantly, no incidence of diabetes. Additional examination revealed that presentation of major histocompatibility complex (MHC) class I epitopes in the pancreatic lymph nodes was absent with a partial impairment of MHC class II presentation. Altogether, this study reveals that CD103+ DCs are essential for autoimmune diabetes development. [Display omitted] •NOD.Batf3−/− mice were generated and validated by microsatellite analysis•NOD.Batf3−/− mice lack CD103+ DCs in islets of Langerhans•Activation of T cells and antigen presentation are deficient in NOD.Batf3−/− mice•NOD.Batf3−/− contain uninflamed islets and never develop type 1 diabetes The earliest events in autoimmune diabetes remain unclear. Ferris et al. demonstrate that an early increase in CD103+ dendritic cells in the islets of Langerhans is coincident with T cell entry. Genetic removal of the CD103+ dendritic cells prevented T cell entry and autoimmunity in nonobese diabetic mice.