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

作者：Yasukawa Shinsuke; Miyazaki Yoshiyuki; Yoshii Chika; Nakaya Mako; Ozaki Naoko; Toda Shuji; Kuroda Etsushi; Ishibashi Ken ichi; Yasuda Tomoharu; Natsuaki Yohei; Mi ichi Fumika; Iizasa Ei' ichi; Nakahara Takeshi; Yamazaki Masanori; Kabashima Kenji; Iwakura Yoichiro; Takai Toshiyuki; Saito Takashi; Kurosaki Tomohiro; Malissen Bernard; Ohno Naohito; Furue Masutaka; Yoshida Hiroki; Hara Hiromitsu^*

来源：Nature Communications, 2014, 5(1): 3755.

DOI：10.1038/ncomms4755

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). Naive 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-1 alpha/beta secretion and their ability to prime Tcells. 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.

• 出版日期2014-5