Type-1-diabetes is an autoimmune disease characterized by destruction of insulin-producing β-cells in the pancreas by autoreactive T cells. An important role for plasmacytoid dendritic cells (pDCs) in this process is increasingly recognized; however, the exact cellular and molecular mechanisms by which pDCs act are poorly understood.
We show that low numbers of pDCs are present in the islets of Langerhans during steady state, and that increasing numbers of pDCs are recruited to the islets during progression of insulitis in the NOD (non-obese diabetic) mouse model of type 1 diabetes. Furthermore, we show reduced incidence of diabetes in conditional E2-2 knock out NOD mice deficient in pDCs. We further demonstrate an altered cellular composition of the insulitic infiltrate as well as delayed kinetics of insulitis in pDC deficient NOD mice. We specifically find that recruitment of Th1 CD4+ T-cells to islets is altered as a consequence of pDC deficiency, further supporting that pDCs are rate limiting for the progression of insulitis. Collectively these results demonstrates a role for pDCs in diabetes development in the NOD mouse and suggest a role for these cells in priming and activating β-cell-reactive cytotoxic T-cells, thereby potentiating the autoimmune destruction of β-cells.