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

• 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

SummaryAutoimmune 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.

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