IκB-ζ Expression Requires Both TYK2/STAT3 Activity and IL-17–Regulated mRNA Stabilization

Muromoto, Ryuta; Tawa, Keisuke; Ohgakiuchi, Yui; Sato, Ami; Saino, Yuka; Hirashima, Koki; Minoguchi, Hiroya; Kitai, Yuichi; Kashiwakura, Jun-ichi; Shimoda, Kazuya; Oritani, Kenji; Matsuda, Tadashi

IκB-ζ Expression Requires Both TYK2/STAT3 Activity and IL-17–Regulated mRNA Stabilization

Muromoto, Ryuta; Tawa, Keisuke; Ohgakiuchi, Yui et al.

ImmunoHorizons, 2019, 3(5), 172-185

Permalink : https://hdl.handle.net/2115/82064

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アクセス権	open access
URI	https://hdl.handle.net/2115/82064
タイトル	IκB-ζ Expression Requires Both TYK2/STAT3 Activity and IL-17–Regulated mRNA Stabilization
著者	Muromoto, Ryuta ; Tawa, Keisuke ; Ohgakiuchi, Yui ; Sato, Ami ; Saino, Yuka ; Hirashima, Koki ; Minoguchi, Hiroya ; Kitai, Yuichi ; Kashiwakura, Jun-ichi ; Shimoda, Kazuya ; Oritani, Kenji ; Matsuda, Tadashi
e-Rad_Researcher 30455597 著者名 Muromoto, Ryuta
著者名 Tawa, Keisuke
著者名 Ohgakiuchi, Yui
著者名 Sato, Ami
著者名 Saino, Yuka
著者名 Hirashima, Koki
著者名 Minoguchi, Hiroya
e-Rad_Researcher 90756165 著者名 Kitai, Yuichi
e-Rad_Researcher 90373290 著者名 Kashiwakura, Jun-ichi
e-Rad_Researcher 90311844 著者名 Shimoda, Kazuya
e-Rad_Researcher 70324762 著者名 Oritani, Kenji
e-Rad_Researcher 20212219 著者名 Matsuda, Tadashi
言語	英語
発行日	2019-05-16
出版者	The American Association of Immunologists
収録物名	ImmunoHorizons
巻(号)	3(5)
ページ	172-185
抄録	Cytokine IL-17A (IL-17) acts on various cell types, including epidermal keratinocytes, and induces antimicrobial peptide and chemokine production to elicit antibacterial and antifungal defense responses. Excess IL-17 leads to inflammatory skin diseases such as psoriasis. The IκB family protein IκB-ζ mediates IL-17–induced responses. However, the mechanism controlling IκB-ζ expression in IL-17–stimulated cells remains elusive. In this study, we showed that JAK kinase TYK2 positively regulates IL-17–induced IκB-ζ expression. TYK2-deficient mice showed reduced inflammation and concomitant reduction of IκB-ζ mRNA compared with wild-type mice in imiquimod-induced skin inflammation. The analysis of the IκB-ζ promoter activity using human cell lines (HaCaT and HeLa) revealed that catalytic activity of TYK2 and its substrate transcription factor STAT3, but not IL-17, is required for IκB-ζ promoter activity. In contrast, IL-17–induced signaling, which did not activate STAT3, posttranscriptionally stabilized IκB-ζ mRNA via its 3′-untranslated region. IL-17 signaling protein ACT1 was required to counteract constitutive IκB-ζ mRNA degradation by RNase Regnase-1. These results suggested that transcriptional activation by TYK2–STAT3 pathway and mRNA stabilization by IL-17–mediated signals act separately from each other but complementarily to achieve IκB-ζ induction. Therefore, JAK/TYK2 inhibition might be of significance in regulation of IL-17–induced inflammatory reactions.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
権利情報	Creative Commons Attribution 4.0 International
EISSN	2573-7732
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.4049/immunohorizons.1900023