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

Author

Listed:
  • Shinsuke Yasukawa

    (Saga Medical School, 5-1-1 Nabeshima Saga, Saga 849-8501, Japan
    Graduate School of Medical Sciences, Kyushu University School of Medicine, 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, 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
    Kobe Pharma Research Institute, Nippon Boehringer Ingelheim)

  • 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
    Laboratory of Lymphocyte Differentiation, WPI Immunology Frontier Research Center (iFREC), Osaka University)

  • 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)

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.

Suggested Citation

  • 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 Iizas, 2014. "An ITAM-Syk-CARD9 signalling axis triggers contact hypersensitivity by stimulating IL-1 production in dendritic cells," Nature Communications, Nature, vol. 5(1), pages 1-14, September.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4755
    DOI: 10.1038/ncomms4755
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