RESEARCH ARTICLE E2-2 Dependent Plasmacytoid Dendritic Cells Control Autoimmune Diabetes

Autoimmune diabetes is a consequence of immune-cell infiltration and destruction of pan-creatic β-cells in the islets of Langerhans. We analyzed the cellular composition of the insu-litic lesions in the autoimmune-prone non-obese diabetic (NOD) mouse and observed a peak in recruitment of plasmacytoid dendritic cells (pDCs) to NOD islets around 8–9 weeks of age. This peak coincides with increased spontaneous expression of type-1-IFN response genes and CpG1585 induced production of IFN-α from NOD islets. The transcription factor E2-2 is specifically required for the maturation of pDCs, and we show that knocking out E2-2 conditionally in CD11c+ cells leads to a reduced recruitment of pDCs to pancreatic islets and reduced CpG1585 induced production of IFN-α during insulitis. As a consequence, insu-litis has a less aggressive expression profile of the Th1 cytokine IFN-γ and a markedly reduced diabetes incidence. Collectively, these observations demonstrate a disease-pro-moting role of E2-2 dependent pDCs in the pancreas during autoimmune diabetes in the NODmouse