Dendritic cells (DCs) contribute to psoriasis pathogenesis. In a mouse model of imiquimod-induced psoriasiform skin inflammation, we found that p38α 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 p38α 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 p38α in LCs specifically promoted IL-17 production from γδ 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 p38α signaling in LCs in promoting inflammatory responses in the skin and suggest that targeting p38α signaling in LCs may offer an effective therapeutic approach to treat psoriasis.

树突状细胞（DC）有助于牛皮癣的发病机理。在咪喹莫特诱导的牛皮癣样皮肤炎症的小鼠模型中，我们发现朗格罕斯细胞（LCs）（DC的皮肤驻留子集）中的p38α活性促进了产生IL-17（一种涉及炎症的细胞因子）的T细胞的生成。在自身免疫性疾病中。LC中p38α的缺失，但其他皮肤或循环DC亚群或T细胞中的p38α的缺失，则减少了小鼠中T细胞介导的牛皮癣样皮肤炎症。LC中p38α的活性可特异性促进γδ和CD4 ⁺产生IL-17通过增加IL-23和IL-6（两种刺激IL-17分泌的细胞因子）的丰度提高T细胞。通过药理学抑制或基因删除抑制p38活性也降低了已建立的牛皮癣样皮肤炎症的严重性。总之，我们的发现表明LC中p38α信号在促进皮肤炎症反应中起着关键作用，并表明靶向LC中p38α信号可能提供治疗牛皮癣的有效治疗方法。