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

Stephen T. Ferris, Javier A. Carrero, James F. Mohan, Boris Calderon, Kenneth M. Murphy, Emil R. Unanue

Research output: Contribution to journalArticlepeer-review

88 Scopus citations

Abstract

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 4weeks of age, CD4+ Tcells 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 Tcells 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.

Original languageEnglish
Pages (from-to)657-669
Number of pages13
JournalImmunity
Volume41
Issue number4
DOIs
StatePublished - Oct 16 2014

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