Research ArticleImmunology

p38α signaling in Langerhans cells promotes the development of IL-17–producing T cells and psoriasiform skin inflammation

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Science Signaling  13 Mar 2018:
Vol. 11, Issue 521, eaao1685
DOI: 10.1126/scisignal.aao1685

p38α signaling in psoriasis

Psoriasis is an autoimmune skin condition that is linked to the proinflammatory cytokines IL-23, which triggers epidermal hyperplasia, and IL-17, which is produced by T cells in the skin. Zheng et al. found that p38α signaling specifically in skin-resident dendritic cells known as Langerhans cells was important for the pathogenesis of psoriasis in a mouse model of the disease. p38α signaling in Langerhans cells stimulated the production of IL-23, which is critical for the development of IL-17–producing T cells that are implicated in the disease. Genetic deletion or pharmacological inhibition of p38α reduced skin inflammation in mice with established psoriatic disease. Together, these data identify an important cellular source of pathogenic IL-23 and suggest that p38α in skin-resident Langerhans cells could be targeted to treat psoriasis.


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.

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