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IL-17A plays a central role in the expression of psoriasis signature genes through the induction of I kappa B-zeta in keratinocytes

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タイトル: IL-17A plays a central role in the expression of psoriasis signature genes through the induction of I kappa B-zeta in keratinocytes
著者: Muromoto, Ryuta 著作を一覧する
Hirao, Toru 著作を一覧する
Tawa, Keisuke 著作を一覧する
Hirashima, Koki 著作を一覧する
Kon, Shigeyuki 著作を一覧する
Kitai, Yuichi 著作を一覧する
Matsuda, Tadashi 著作を一覧する
キーワード: cytokine
epidermal keratinocyte
発行日: 2016年 9月
出版者: Oxford University Press
誌名: International immunology
巻: 28
号: 9
開始ページ: 443
終了ページ: 452
出版社 DOI: 10.1093/intimm/dxw011
抄録: In psoriasis lesions, a diverse mixture of cytokines is up-regulated that influence each other generating a complex inflammatory situation. Although this is the case, the inhibition of IL-17A alone showed unprecedented clinical results in patients, indicating that IL-17A is a critical inducer of psoriasis pathogenesis. To elucidate IL-17A-driven keratinocyte-intrinsic signaling pathways, we treated monolayers of normal human epidermal keratinocytes in vitro with a mixture of six cytokines (IL-17A, TNF-alpha, IL-17C, IL-22, IL-36. and IFN-gamma) involved in psoriasis to mimic the inflammatory milieu in psoriasis lesions. Microarray and gene set enrichment analysis revealed that this cytokine mixture induced similar gene expression changes with the previous transcriptome studies using psoriasis lesions. Importantly, we identified a set of IL-17A-regulated genes in keratinocytes, which recapitulate typical psoriasis genes exemplified by DEFB4A, S100A7, IL19 and CSF3, based on the differences in the expression profiles of cells stimulated with six cytokines versus cells stimulated with only five cytokines lacking IL-17A. Furthermore, a specific IL-17A-induced gene, NFKBIZ, which encodes I kappa B-zeta, a transcriptional regulator for NF-kappa B, was demonstrated to have a significant role for IL-17A-induced gene expression. Thus, we present novel in vitro data from normal human keratinocytes that would help elucidating the IL-17A-driven keratinocyte activation in psoriasis.
Rights: This is a pre-copyedited, author-produced PDF of an article accepted for publication in International immunology following peer review. The version of record Int. Immunol. (2016) 28(9):443-452, is available online at:
資料タイプ: article (author version)
出現コレクション:雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

提供者: 室本 竜太


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