? 2015 Hansen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Autoimmune diabetes is a consequence of immune-cell infiltration and destruction of pancreatic ?-cells in the islets of Langerhans. We analyzed the cellular composition of the insulitic 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-? 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-? during insulitis. As a consequence, insulitis has a less aggressive expression profile of the Th1 cytokine IFN-? and a markedly reduced diabetes incidence. Collectively, these observations demonstrate a disease-promoting role of E2-2 dependent pDCs in the pancreas during autoimmune diabetes in the NOD mouse.
Hansen, L., Schmidt-Christensen, A., Gupta, S., Fransén-Pettersson, N., Hannibal, T. D., Reizis, B., … Holmberg, D. (2015). E2-2 dependent plasmacytoid dendritic cells control autoimmune diabetes. PLoS ONE, 10(12). https://doi.org/10.1371/journal.pone.0144090