| First Author | Zheng T | Year | 2018 |
| Journal | Sci Signal | Volume | 11 |
| Issue | 521 | PubMed ID | 29535261 |
| Mgi Jnum | J:259233 | Mgi Id | MGI:6142364 |
| Doi | 10.1126/scisignal.aao1685 | Citation | Zheng T, et al. (2018) p38alpha signaling in Langerhans cells promotes the development of IL-17-producing T cells and psoriasiform skin inflammation. Sci Signal 11(521) |
| abstractText | Dendritic cells (DCs) contribute to psoriasis pathogenesis. In a mouse model of imiquimod-induced psoriasiform skin inflammation, we found that p38alpha activity in Langerhans cells (LCs), a skin-resident subset of DCs, promoted the generation of T cells that produce IL-17, a proinflammatory cytokine that is implicated in autoimmune disease. Deletion of p38alpha in LCs, but not in other skin or circulating DC subsets or T cells, decreased T cell-mediated psoriasiform skin inflammation in mice. The activity of p38alpha in LCs specifically promoted IL-17 production from gammadelta and CD4(+) T cells by increasing the abundance of IL-23 and IL-6, two cytokines that stimulate IL-17 secretion. Inhibition of p38 activity through either pharmacological inhibition or genetic deletion also reduced the severity of established psoriasiform skin inflammation. Together, our findings indicate a critical role for p38alpha signaling in LCs in promoting inflammatory responses in the skin and suggest that targeting p38alpha signaling in LCs may offer an effective therapeutic approach to treat psoriasis. |
