Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/34968
Title: IL-17 drives psoriatic inflammation via distinct, target cell-specific mechanisms
Authors: Hye Lin Ha
Hongshan Wang
Prapaporn Pisitkun
Jin Chul Kim
Ilaria Tassi
Wanhu Tang
Maria I. Morasso
Mark C. Udey
Ulrich Siebenlist
National Institute of Allergy and Infectious Diseases
National Institute of Arthritis and Musculoskeletal and Skin Diseases
National Cancer Institute
Mahidol University
Keywords: Multidisciplinary
Issue Date: 19-Aug-2014
Citation: Proceedings of the National Academy of Sciences of the United States of America. Vol.111, No.33 (2014)
Abstract: Psoriasis is a chronic inflammatory skin disease characterized by abnormal keratinocyte proliferation and differentiation and by an influx of inflammatory cells. The mechanisms underlying psoriasis in humans and in mouse models are poorly understood, although evidence strongly points to crucial contributions of IL-17 cytokines, which signal via the obligatory adaptor CIKS/Act1. Here we identify critical roles of CIKS/Act1-mediated signaling in imiquimod-induced psoriatic inflammation, a mouse model that shares features with the human disease. We found that IL-17 cytokines/CIKS-mediated signaling into keratinocytes is essential for neutrophilic microabscess formation and contributes to hyperproliferation and markedly attenuated differentiation of keratinocytes, at least in part via direct effects. In contrast, IL-17 cytokines/CIKS-mediated signaling into nonkeratinocytes, particularly into dermal fibroblasts, promotes cellular infiltration and, importantly, leads to enhanced the accumulation of IL-17-producing γδT cells in skin, comprising a positive feed-forward mechanism. Thus, CIKS-mediated signaling is central in the development of both dermal and epidermal hallmarks of psoriasis, inducing distinct pathologies via target cell-specific effects. CIKS-mediated signaling represents a potential therapeutic target in psoriasis.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84906311286&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/34968
ISSN: 10916490
00278424
Appears in Collections:Scopus 2011-2015

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