Editors' ChoiceImmunology

Antiviral Skin Helpers

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Sci. Signal.  01 Oct 2013:
Vol. 6, Issue 295, pp. ec237
DOI: 10.1126/scisignal.2004769

Psoriasis and atopic dermatitis are common chronic skin diseases characterized by impaired barrier function of the skin, but only atopic dermatitis patients show a high incidence of skin infections. The difference in patients with these two types of skin disorders in the ability to fight bacterial infection has been investigated (see the Perspective by Clark). Wolk et al. identified a mechanism that could produce differences in susceptibility to viral infection. The abundance of four antiviral protein (AVP) transcripts and proteins was greater in the epidermis and keratinocytes in psoriatic lesions compared with atopic dermatitis lesions, nonlesional skin from psoriatic patients, and healthy skin. Of 30 cytokines, only the transcript abundance of interleukin-29 (IL-29), a cytokine that mediates antiviral immune responses, showed a significantly positive correlation with that of all four AVP transcripts in psoriatic lesions. Treating skin explants from healthy donors with recombinant IL-29 increased the abundance of AVP transcripts, whereas treating psoriatic lesion biopsies with an antibody against IL-29 decreased their abundance, suggesting that IL-29 stimulates the production of AVPs in psoriatic lesions. Although IL-29 is produced by plasmacytoid dendritic cells, this cell type was rare in psoriatic lesions. However, the abundance of IL-29 transcripts correlated with that of immune mediators secreted by T helper 17 (TH17) cells, and IL-29 colocalized with the nuclear receptor and transcription factor RORγt, which promotes TH17 cell differentiation. In a panel of cultured T cell subsets, TH17 cell cultures had the greatest amount of IL-29 transcript and secreted protein, and other cytokine profiles in TH17 cultures were similar to those of psoriatic lesions. Generation of IL-29–producing TH17 cells required both RORγt and transforming growth factor–β (TGF-β), and secretion of IL-29 in TH17 cultures was reduced by pharmacological inhibition of either calcineurin or c-Jun N-terminal kinase (JNK), suggesting that RORγt, TGF-β, calcineurin, and JNK are involved in the production of IL-29–secreting TH17 cells. Culturing keratinocytes in conditioned medium from TH17 cells increased the transcript abundance of AVPs. These findings indicate that the secretion of IL-29 by TH17 cells induces AVP-mediated viral defense in psoriatic patients and suggest that IL-29 may be useful in preventing viral infection in atopic dermatitis.

K. Wolk, K. Witte, E. Witte, M. Raftery, G. Kokolakis, S. Philipp, G. Schönrich, K. Warszawska, S. Kirsch, S. Prösch, W. Sterry, H.-D. Volk, R. Sabat, IL-29 is produced by TH17 cells and mediates the cutaneous antiviral competence in psoriasis. Sci. Transl. Med. 5, 204ra129 (2013). [PubMed]

R. A. Clark, Human skin in the game. Sci. Transl. Med. 5, 204ps13 (2013). [PubMed]