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Interleukin-22, a TH17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis


Psoriasis is a chronic inflammatory skin disease characterized by hyperplasia of the epidermis (acanthosis), infiltration of leukocytes into both the dermis and epidermis, and dilation and growth of blood vessels1. The underlying cause of the epidermal acanthosis in psoriasis is still largely unknown. Recently, interleukin (IL)-23, a cytokine involved in the development of IL-17-producing T helper cells (TH17 cells)2,3, was found to have a potential function in the pathogenesis of psoriasis4,5. Here we show that IL-22 is preferentially produced by TH17 cells and mediates the acanthosis induced by IL-23. We found that IL-23 or IL-6 can directly induce the production of IL-22 from both murine and human naive T cells. However, the production of IL-22 and IL-17 from TH17 cells is differentially regulated. Transforming growth factor-β, although crucial for IL-17 production, actually inhibits IL-22 production. Furthermore, IL-22 mediates IL-23-induced acanthosis and dermal inflammation through the activation of Stat3 (signal transduction and activators of transcription 3) in vivo. Our results suggest that TH17 cells, through the production of both IL-22 and IL-17, might have essential functions in host defence and in the pathogenesis of autoimmune diseases such as psoriasis. IL-22, as an effector cytokine produced by T cells, mediates the crosstalk between the immune system and epithelial cells.

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Figure 1: IL-22 is a new effector cytokine downstream of IL-23.
Figure 2: Differential regulation of IL-22 and IL-17 production from CD4 + T cells.
Figure 3: IL-12 and IL-23 both induce acanthosis and inflammation in mouse ear skin, but elicit distinct cytokine profiles.
Figure 4: IL-22 deficiency decreases IL-23-induced ear skin acanthosis and inflammation.


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We thank A. Chan, H. Spits, M. Townsend, J. Grogan and B. Irving for critical suggestions, and W. Lee, C. Olsson, J. Starks, L. Gilmour, M. Hamilton, L. Hall and the Genentech Histology and Immunohistochemistry Laboratories for technical assistance.

Author Contributions Y.Z. performed most of the experimental work. D.M.D., I.K. and J.E.-A. provided all the histology data analyses. P.V. conducted the in vitro experiments with mouse monocytes and human T cells. J.W. developed the assays for IL-22 ELISA and intracellular staining, and genotyped the IL-22 knockout mice. W.O. devised and planned the project, and the manuscript was written by Y.Z., D.M.D. and W.O.

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Correspondence to Wenjun Ouyang.

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COMPETING INTERESTS All authors are employed by Genentech, Inc.

Supplementary information

Supplementary Information

This file contains Supplementary Figures and Legends 1-8; Supplementary Methods. Supplementary Figure S1 shows IL-22 production from various IL-23 activated lymphocytes. Supplementary Figure S2 shows IL-22 production from human T cells. Supplementary Figure S3 shows IL-12 and IL-23 induce thickness of mouse ears. Supplementary Figure S4 shows targeted disruption of murine IL-22 gene. Supplementary Figure S5 shows IL-19, IL-20 and IL-24 mRNA expression in IL-12 or IL-23 treated mouse ears. Supplementary Figure S6 shows the effect of IL-22 blockade on IL-23 induced ear skin inflammation. Supplementary Figure S7 shows blockade of IL-22 has no effect on IL-12 induced ear skin inflammation. Supplementary Figure S8 shows IHC staining of T cells, neutrophils and keratin 6 in IL-23 treated IL-22-/- or wildtype mice. The Supplementary Methods provide details on the experimental procedures. (PDF 2556 kb)

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Zheng, Y., Danilenko, D., Valdez, P. et al. Interleukin-22, a TH17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. Nature 445, 648–651 (2007).

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