| First Author | Huang G | Year | 2015 |
| Journal | Sci Signal | Volume | 8 |
| Issue | 366 | Pages | ra24 |
| PubMed ID | 25737586 | Mgi Jnum | J:259542 |
| Mgi Id | MGI:6142030 | Doi | 10.1126/scisignal.aaa2147 |
| Citation | Huang G, et al. (2015) Control of IL-17 receptor signaling and tissue inflammation by the p38alpha-MKP-1 signaling axis in a mouse model of multiple sclerosis. Sci Signal 8(366):ra24 |
| abstractText | T helper 17 (T(H)17) cells, a subset of CD4+ T cells that secrete the proinflammatory cytokine interleukin-17 (IL-17), play a key pathogenic role in autoimmune diseases. Through inducible and tissue-specific deletion systems, we described the time- and tissue-specific roles of the mitogen-activated protein kinase (MAPK) p38alpha in mediating T(H)17 cell-induced tissue inflammation. Inducible deletion of Mapk14 (which encodes p38alpha) after the onset of experimental autoimmune encephalomyelitis (EAE), a murine model for human multiple sclerosis, protected mice from inflammation. Furthermore, the severity of EAE was markedly reduced in mice with specific loss of p38alpha in neuroectoderm-derived cells, including astrocytes, an effect that was associated with defective production of chemokines and decreased infiltration of the target tissue by immune cells. p38alpha linked IL-17 receptor (IL-17R) signaling to the expression of genes encoding proinflammatory chemokines and cytokines. Mice that lacked MAPK phosphatase 1 (MKP-1), an inhibitor of p38alpha, had exacerbated EAE and enhanced expression of IL-17R-dependent genes. Our results suggest that the p38alpha-MKP-1 signaling axis links IL-17R signaling in tissue-resident cells to autoimmune inflammation dependent on infiltrating T(H)17 cells. |
