Research ArticlePsoriasis

IL-29 Is Produced by TH17 Cells and Mediates the Cutaneous Antiviral Competence in Psoriasis

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Science Translational Medicine  25 Sep 2013:
Vol. 5, Issue 204, pp. 204ra129
DOI: 10.1126/scitranslmed.3006245

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Psoriasis and atopic dermatitis (AD) are the most common chronic inflammatory skin diseases. Although both patient groups show strongly impaired skin barrier function, only AD patients frequently suffer from cutaneous viral infections. The mechanisms underlying the distinct susceptibilities to these pathogenetic and often life-threatening infections are unknown. We show that antiviral proteins (AVPs) such as MX1, BST2, ISG15, and OAS2 were strongly elevated in psoriatic compared to AD lesions and healthy skin. Of 30 individually quantified cytokines in psoriatic lesions, interleukin-29 (IL-29) was the only mediator whose expression correlated with the AVP levels. IL-29 was absent in AD lesions, and neutralization of IL-29 in psoriatic skin reduced AVP expression. Accordingly, IL-29 raised AVP levels in isolated keratinocytes, epidermis models, and human skin explants, but did not influence antibacterial protein production. AVP induction correlated with increased antiviral defense of IL-29–treated keratinocytes. Furthermore, IL-29 elevated the expression of signaling elements, resulting in increased sensitivity of keratinocytes toward its own action. We identified T helper 17 (TH17) cells as IL-29 producers and demonstrated their ability to increase the antiviral competence of keratinocytes in an IL-29–dependent manner. Transforming growth factor–β and the activity of RORγt/RORα were most critical for the development of IL-29–producing TH17 cells. IL-29 secretion by these cells was dependent on NFAT and c-Jun N-terminal kinase and was inhibited by IL-4. These data suggest that TH17 cell–derived IL-29, which is absent in AD, mediates the robust antiviral state on psoriatic skin, and demonstrate a new function of TH17 cells.

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