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

Research output: Contribution to journalArticle

37 Citations (Scopus)

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 /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.

Original languageEnglish
Article number3755
JournalNature communications
Volume5
DOIs
Publication statusPublished - May 7 2014

Fingerprint

spleen
Haptens
tyrosine
Contact Dermatitis
interleukins
Caspases
Protein-Tyrosine Kinases
Dendritic Cells
Interleukin-1
actuators
secretions
T-cells
proteins
cells
Proteins
T-Lymphocytes
contact dermatitis
Chemical activation
Dermatitis
activation

All Science Journal Classification (ASJC) codes

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

Cite this

An ITAM-Syk-CARD9 signalling axis triggers contact hypersensitivity by stimulating il-1 production in dendritic cells. / 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, Eíichi; Nakahara, Takeshi; Yamazaki, Masanori; Kabashima, Kenji; Iwakura, Yoichiro; Takai, Toshiyuki; Saito, Takashi; Kurosaki, Tomohiro; Malissen, Bernard; Ohno, Naohito; Furue, Masutaka; Yoshida, Hiroki; Hara, Hiromitsu.

In: Nature communications, Vol. 5, 3755, 07.05.2014.

Research output: Contribution to journalArticle

Yasukawa, S, Miyazaki, Y, Yoshii, C, Nakaya, M, Ozaki, N, Toda, S, Kuroda, E, Ishibashi, KI, Yasuda, T, Natsuaki, Y, Mi-Ichi, F, Iizasa, E, Nakahara, T, Yamazaki, M, Kabashima, K, Iwakura, Y, Takai, T, Saito, T, Kurosaki, T, Malissen, B, Ohno, N, Furue, M, Yoshida, H & Hara, H 2014, 'An ITAM-Syk-CARD9 signalling axis triggers contact hypersensitivity by stimulating il-1 production in dendritic cells', Nature communications, vol. 5, 3755. https://doi.org/10.1038/ncomms4755
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, Eíichi ; Nakahara, Takeshi ; Yamazaki, Masanori ; Kabashima, Kenji ; Iwakura, Yoichiro ; Takai, Toshiyuki ; Saito, Takashi ; Kurosaki, Tomohiro ; Malissen, Bernard ; Ohno, Naohito ; Furue, Masutaka ; Yoshida, Hiroki ; Hara, Hiromitsu. / An ITAM-Syk-CARD9 signalling axis triggers contact hypersensitivity by stimulating il-1 production in dendritic cells. In: Nature communications. 2014 ; Vol. 5.
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AU - Kurosaki, Tomohiro

AU - Malissen, Bernard

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