p38- signaling in Langerhans cells promotes thedevelopment of IL-17–producing T cells andpsoriasiform skin inflammation

摘要

Dendritic cells (DCs) contribute to psoriasis pathogenesis. In a mouse model of imiquimod-induced psoriasiformskin inflammation, we found that p38- activity in Langerhans cells (LCs), a skin-resident subset of DCs, promotedthe generation of T cells that produce IL-17, a proinflammatory cytokine that is implicated in autoimmune disease.Deletion of p38- in LCs, but not in other skin or circulating DC subsets or T cells, decreased T cell–mediatedpsoriasiform skin inflammation in mice. The activity of p38- in LCs specifically promoted IL-17 production from -and CD4+T cells by increasing the abundance of IL-23 and IL-6, two cytokines that stimulate IL-17 secretion. Inhibitionof p38 activity through either pharmacological inhibition or genetic deletion also reduced the severity ofestablished psoriasiform skin inflammation. Together, our findings indicate a critical role for p38- signaling in LCsin promoting inflammatory responses in the skin and suggest that targeting p38 signaling in LCs may offer aneffective therapeutic approach to treat psoriasis.