An ITAM-Syk-CARD9 signalling axis triggers contact hypersensitivity by stimulating il-1 production in dendritic cells

Shinsuke Yasukawa, Yoshiyuki Miyazaki, Chika Yoshii, Mako Nakaya, Naoko Ozaki, Shuji Toda, Etsushi Kuroda, Ken Ichi Ishibashi, Tomoharu Yasuda, Yohei Natsuaki, Fumika Mi-Ichi, Eíichi Iizasa, Takeshi Nakahara, Masanori Yamazaki, Kenji Kabashima, Yoichiro Iwakura, Toshiyuki Takai, Takashi Saito, Tomohiro Kurosaki, Bernard MalissenNaohito Ohno, Masutaka Furue, Hiroki Yoshida, Hiromitsu Hara

研究成果: ジャーナルへの寄稿記事

38 引用 (Scopus)

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A variety of reactive organic compounds, called haptens, can cause allergic contact dermatitis. However, the innate immune mechanisms by which haptens stimulate dendritic cells (DCs) to sensitize T cells remain unclear. Here we show that the coupling of ITAM-Syk-CARD9 signalling to interleukin-1 (IL-1) secretion in DCs is crucial for allergic sensitization to haptens. Both MyD88 and Caspase recruitment domain-containing protein 9 (CARD9) signalling are required for contact hypersensitivity (CHS). Naïve T cells require signals received through IL-1R1-MyD88 for effector differentiation, whereas DCs require CARD9 and spleen tyrosine kinase (Syk) signalling for hapten-induced IL-1α /Î 2 secretion and their ability to prime T cells. DC-specific deletion of CARD9, DAP12, Syk or NLRP3, but not MyD88, is sufficient to abolish CHS. All tested haptens, but not irritants, can induce Syk activation, leading to both the CARD9/BCL10-dependent pro-IL-1 synthesis (signal1) and reactive oxygen species-mediated NLRP3 inflammasome activation (signal2), required for IL-1 secretion. These data unveil an innate immune mechanism crucial for allergic contact sensitization to chemical compounds.

元の言語英語
記事番号3755
ジャーナルNature communications
5
DOI
出版物ステータス出版済み - 5 7 2014

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All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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