| First Author | Hansen L | Year | 2015 |
| Journal | PLoS One | Volume | 10 |
| Issue | 12 | Pages | e0144090 |
| PubMed ID | 26624013 | Mgi Jnum | J:244811 |
| Mgi Id | MGI:5913590 | Doi | 10.1371/journal.pone.0144090 |
| Citation | Hansen L, et al. (2015) E2-2 Dependent Plasmacytoid Dendritic Cells Control Autoimmune Diabetes. PLoS One 10(12):e0144090 |
| abstractText | Autoimmune diabetes is a consequence of immune-cell infiltration and destruction of pancreatic beta-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-alpha 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-alpha during insulitis. As a consequence, insulitis has a less aggressive expression profile of the Th1 cytokine IFN-gamma 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. |
