CIKS/Act1-mediated signaling by IL-17 cytokines in context: implications for how a CIKS gene variant may predispose to psoriasis.

The Journal of Immunology : Official Journal of the American Association of Immunologists
Søren Ulrik SønderUlrich Siebenlist

Abstract

Psoriasis is a relapsing skin disease characterized by abnormal keratinocyte proliferation and differentiation and by an influx of inflammatory immune cells. Recently, IL-17 cytokines have been strongly implicated as critical for the pathogenesis of this disease. IL-17A (also known as IL-17) and IL-17F are the signature cytokines of Th17 cells, but are also produced by innate cells, including γδ T cells present in skin, whereas epithelial cells, including keratinocytes, may produce IL-17C. IL-17 cytokines signal via the adaptor protein connection to IκB kinase and stress-activated protein kinases (CIKS)/Act1. Psoriasis is a disease with a strong genetic predisposition, and the gene encoding CIKS has recently been identified as a susceptibility locus. Unexpectedly, one predisposing gene variant features a mutation that impairs rather than enhances CIKS-mediated IL-17 cytokine signaling, counter to the predicted role for IL-17 cytokines in psoriatic inflammation. In this study, we demonstrate, however, that this mutant adaptor does not impair the IL-17-specific contributions to the genetic response when combined with TNF-α, a cytokine also prominent in psoriatic inflammation. Interestingly, TNF-α signals compensate IL-17 signalin...Continue Reading

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Citations

Aug 6, 2014·Proceedings of the National Academy of Sciences of the United States of America·Hye-Lin HaUlrich Siebenlist
Oct 16, 2015·Proceedings of the National Academy of Sciences of the United States of America·Claus JohansenLars Iversen
Mar 4, 2017·Trends in Immunology·Nilesh AmatyaSarah L Gaffen
Dec 7, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Leticia MoninSarah L Gaffen
Apr 18, 2015·Clinical and Translational Medicine·William R SwindellJohann E Gudjonsson
May 8, 2020·Clinical and Experimental Immunology·J M FletcherC M Smith
Feb 25, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Domenico SommaAntonio Leonardi
Jul 16, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ling WuXiaoxia Li

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