Accessory protein-like is essential for IL-18-mediated signaling

Heidi Cheung, Nien Jung Chen, Zhaodan Cao, Nobuyuki Ono, Pamela S. Ohashi, Wen Chen Yeh

研究成果: Contribution to journalArticle査読

52 被引用数 (Scopus)

抄録

IL-18 is an essential cytokine for both innate and adaptive immunity. Signaling by IL-18 requires IL-18Rα, which binds specifically to the ligand and contains sequence homology to IL-1R and TLRs. It is well established that IL-1R signaling requires an accessory cell surface protein, AcP. Other accessory proteins also exist with roles in regulating TLR signaling, but some have inhibitory functions. An AcP-like molecule (AcPL) has been identified with the ability to cooperate with IL-18Rα in vitro; however, the physiological function of AcPL remains unknown. In this study, we demonstrate that IL-18 signals are abolished in AcPL-deficient mice and cells. Splenocytes from mutant mice fail to respond to IL-18-induced proliferation and IFN-γ production. In particular, Th1 cells lacking AcPL fail to produce IFN-γ in response to IL-18. AcPL-deficient neutrophils also fail to respond to IL-18-induced activation and cytokine production. Furthermore, AcPL is required for NK-mediated cytotoxicity induced by in vivo IL-18 stimulation. However, AcPL is dispensable for the activation or inhibition of IL-1R and the various TLR signals that we have examined. These results suggest that AcPL is a critical and specific cell surface receptor that is required for IL-18 signaling.

本文言語英語
ページ(範囲)5351-5357
ページ数7
ジャーナルJournal of Immunology
174
9
DOI
出版ステータス出版済み - 5 1 2005
外部発表はい

All Science Journal Classification (ASJC) codes

  • 免疫アレルギー学
  • 免疫学

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