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

Abstract

Summary Autoimmune diabetes is characterized by inflammatory infiltration; however the initiating events are poorly understood. We found that the islets of Langerhans in young non-obese diabetic (NOD) mice contained two antigen presenting cell (APC) populations: a major macrophage and a minor CD103+ dendritic cell (DC) population. By four weeks of age, CD4+ T cells entered islets coincident with an increase of 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 were essential for autoimmune diabetes development.

ω-3 polyunsaturated fatty acids ameliorate type 1 diabetes and autoimmunity

“…No spontaneous reversal to less than 11.11 mmol/l was observed in any of the control groups (n = 15 per group). Consistent with results reported by others (26,27), we found that 80% of female NOD mice on a regular diet devel-IL-10 (21). The intervention of dysregulated Th cells is therefore critical to stopping autoimmune progression and the inflammatory attack against β cells.…”

Beta cells transfer vesicles containing insulin to phagocytes for presentation to T cells

“…Islets were isolated following standard procedures described before (11). In brief, collagenase was injected into the pancreas via the common bile duct, after which islets were selected under microscopy with a pipettor.…”

“…In the absence of macrophages, islets are of much smaller size, suggesting a trophic effect of macrophages on islets (12,30,31). We envision a symbiotic interaction between both cells: Experiments in progress indicate that islet macrophages are in an activated state (11,31).…”

“…Altogether, a persuasive case has been made for insulin autoreactivity as driving forward diabetic autoimmunity (6)(7)(8)(9)(10). Our previous investigations showed that the islets of Langerhans of NOD mice contained resident phagocytes represented by two lineages: typical macrophages composed the majority, whereas a minority was made up of a subset of dendritic cells (DCs) expressing the CD103 integrinthat is, the CD103 + /CD8α + DC lineage under the control of the Batf3 transcription factor (11). Islet phagocytes were found to be in intimate contact with both beta cells and the vessel walls, throwing small projections into the vessel lumen (12).…”

“…It is likely that the node is supplied by the movement of islet phagocytes. Recently we reported the seminal role of the CD103 + DCs in such a process (11).…”