| First Author | Stockenhuber K | Year | 2018 |
| Journal | J Exp Med | Volume | 215 |
| Issue | 8 | Pages | 1987-1998 |
| PubMed ID | 29980582 | Mgi Jnum | J:271275 |
| Mgi Id | MGI:6201968 | Doi | 10.1084/jem.20172094 |
| Citation | Stockenhuber K, et al. (2018) Foxp3(+) T reg cells control psoriasiform inflammation by restraining an IFN-I-driven CD8(+) T cell response. J Exp Med 215(8):1987-1998 |
| abstractText | Psoriasis is a complex inflammatory skin disease affecting approximately 3% of the population worldwide. Although type I interferons (IFN-I) are thought to be involved in its pathogenesis, the details of this relationship remain elusive. Here we show that in a murine model of imiquimod-driven psoriatic skin inflammation, Foxp3(+) regulatory T cells (T reg cells) control inflammation severity by restraining IFN-I. Depletion of T reg cells induces IFN-I and IFN-stimulated gene expression, and leads to accumulation of CD8(+) T cells in lesional skin. Mononuclear phagocytes (MNPs) were the source of IFN-I, and their depletion reversed the effect of T reg cell depletion. Blockade of IFN-I signaling abolished CD8(+) T cell infiltration and excess inflammation in the skin of T reg cell-depleted mice. Depletion of CD8(+) T cells attenuated pathology, confirming their role as critical effector cells downstream of IFN-I. Our results describe an unexpected role for T reg cells in restraint of an MNP-IFN-I-driven CD8(+) T cell response during psoriasiform skin inflammation. These findings highlight a pathway with potential relevance for the treatment of early-stage disease. |
