These authors contributed equally to the study.
IL-22 regulates the expression of genes responsible for antimicrobial defense, cellular differentiation, and mobility in keratinocytes: a potential role in psoriasis
Article first published online: 18 APR 2006
Copyright © 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
European Journal of Immunology
Volume 36, Issue 5, pages 1309–1323, May 2006
How to Cite
Wolk, K., Witte, E., Wallace, E., Döcke, W.-D., Kunz, S., Asadullah, K., Volk, H.-D., Sterry, W. and Sabat, R. (2006), IL-22 regulates the expression of genes responsible for antimicrobial defense, cellular differentiation, and mobility in keratinocytes: a potential role in psoriasis. Eur. J. Immunol., 36: 1309–1323. doi: 10.1002/eji.200535503
- Issue published online: 25 APR 2006
- Article first published online: 18 APR 2006
- Manuscript Accepted: 9 MAR 2006
- Manuscript Revised: 7 FEB 2006
- Manuscript Received: 17 SEP 2005
IL-22 is an IFN–IL-10 cytokine family member, which is produced by activated Th1 and NK cells and acts primarily on epithelial cells. Here we demonstrate that IL-22, in contrast to its relative IFN-γ, regulates the expression of only a few genes in keratinocytes. This is due to varied signal transduction. Gene expressions regulated by IL-22 should enhance antimicrobial defense [psoriasin (S100A7), calgranulin A (S100A8), calgranulin B (S100A9)], inhibit cellular differentiation (e.g., profilaggrin, keratins 1 and 10, kallikrein 7), and increase cellular mobility [e.g., matrix metalloproteinease 1 (MMP1, collagenase 1), MMP3 (stromelysin 1), desmocollin 1]. In contrast, IFN-γ favored the expression of MHC pathway molecules, adhesion molecules, cytokines, chemokines, and their receptors. The IL-22 effects were transcriptional and either independent of protein synthesis and secretion, or mediated by a secreted protein. Inflammatory conditions, but not keratinocyte differentiation, amplified the IL-22 effects. IL-22 application in mice enhanced cutaneous S100A9 and MMP1 expression. High IL-22 levels in psoriatic skin were associated with strongly up-regulated cutaneous S100A7, S100A8, S100A9, and MMP1 expression. Psoriatic patients showed strongly elevated IL-22 plasma levels, which correlated with the disease severity. Expression of IL-22 and IL-22-regulated genes was reduced by anti-psoriatic therapy. In summary, despite similarities, IFN-γ primarily amplifies inflammation, while IL-22 may be important in the innate immunity and reorganization of epithelia.