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, Ei’ichi Iizasa, Takeshi Nakahara, Masanori Yamazaki, Kenji Kabashima, Yoichiro Iwakura, Toshiyuki Takai, Takashi Saito, Tomohiro Kurosaki, Bernard Malissen, Naohito Ohno, Masutaka Furue, Hiroki Yoshida and Hiromitsu Hara ()
Additional contact information
Shinsuke Yasukawa: Saga Medical School, 5-1-1 Nabeshima Saga, Saga 849-8501, Japan
Yoshiyuki Miyazaki: Saga Medical School, 5-1-1 Nabeshima Saga, Saga 849-8501, Japan
Chika Yoshii: Graduate School of Medical Sciences, Kyushu University School of Medicine, 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan
Mako Nakaya: Saga Medical School, 5-1-1 Nabeshima Saga, Saga 849-8501, Japan
Naoko Ozaki: Saga Medical School, 5-1-1 Nabeshima Saga, Saga 849-8501, Japan
Shuji Toda: Saga Medical School, 5-1-1 Nabeshima Saga, Saga 849-8501, Japan
Etsushi Kuroda: Laboratory of Vaccine Science, WPI Immunology Frontier Research Center (IFREC), Osaka University
Ken-ichi Ishibashi: Laboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy & Life Sciences
Tomoharu Yasuda: Laboratory for Lymphocyte Differentiation, RIKEN Reserach Center for Allergy and Immunology
Yohei Natsuaki: Kyoto University Graduate School of Medicine, 54 Shogoin-Kawara Sakyo, Kyoto 606-8507, Japan
Fumika Mi-ichi: Saga Medical School, 5-1-1 Nabeshima Saga, Saga 849-8501, Japan
Ei’ichi Iizasa: Saga Medical School, 5-1-1 Nabeshima Saga, Saga 849-8501, Japan
Takeshi Nakahara: Graduate School of Medical Sciences, Kyushu University School of Medicine, 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan
Masanori Yamazaki: Saga Medical School, 5-1-1 Nabeshima Saga, Saga 849-8501, Japan
Kenji Kabashima: Kyoto University Graduate School of Medicine, 54 Shogoin-Kawara Sakyo, Kyoto 606-8507, Japan
Yoichiro Iwakura: Research Institute for Biomedical Sciences, Tokyo University of Science
Toshiyuki Takai: Institute of Development, Aging and Cancer, Tohoku University
Takashi Saito: Laboratory for Cell Signaling, RIKEN Research Center for Allergy and Immunology
Tomohiro Kurosaki: Laboratory for Lymphocyte Differentiation, RIKEN Reserach Center for Allergy and Immunology
Bernard Malissen: Centre d’Immunologie de Marseille-Luminy, Parc Scientifique de Marseille-Luminy
Naohito Ohno: Laboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy & Life Sciences
Masutaka Furue: Graduate School of Medical Sciences, Kyushu University School of Medicine, 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan
Hiroki Yoshida: Saga Medical School, 5-1-1 Nabeshima Saga, Saga 849-8501, Japan
Hiromitsu Hara: Saga Medical School, 5-1-1 Nabeshima Saga, Saga 849-8501, Japan

Nature Communications, 2014, vol. 5, issue 1, 1-14

Abstract: Abstract 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/β 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.

Date: 2014
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DOI: 10.1038/ncomms4755

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