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 Malissen; Naohito Ohno; Masutaka Furue; Hiroki Yoshida; Hiromitsu Hara

doi:10.1038/ncomms4755

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

Division of Aging Science

Research output: Contribution to journal › Article › peer-review

64 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-1Î± /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 language	English
Article number	3755
Journal	Nature communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms4755
Publication status	Published - 2014 May 7

ASJC Scopus subject areas

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

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10.1038/ncomms4755

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Yasukawa, S., Miyazaki, Y., Yoshii, C., Nakaya, M., Ozaki, N., Toda, S., Kuroda, E., Ishibashi, K. I., Yasuda, T., Natsuaki, Y., Mi-Ichi, F., Iizasa, E., Nakahara, T., Yamazaki, M., Kabashima, K., Iwakura, Y., Takai, T., Saito, T., Kurosaki, T., ... Hara, H. (2014). An ITAM-Syk-CARD9 signalling axis triggers contact hypersensitivity by stimulating il-1 production in dendritic cells. Nature communications, 5, [3755]. https://doi.org/10.1038/ncomms4755

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

@article{23215437b2e3482a870cd7142bf80a14,

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

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). Na{\"i}ve 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{\^I}± /{\^I} 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.",

author = "Shinsuke Yasukawa and Yoshiyuki Miyazaki and Chika Yoshii and Mako Nakaya and Naoko Ozaki and Shuji Toda and Etsushi Kuroda and Ishibashi, {Ken Ichi} and Tomoharu Yasuda and Yohei Natsuaki and Fumika Mi-Ichi and E{\'i}ichi Iizasa and Takeshi Nakahara and Masanori Yamazaki and Kenji Kabashima and Yoichiro Iwakura and Toshiyuki Takai and Takashi Saito and Tomohiro Kurosaki and Bernard Malissen and Naohito Ohno and Masutaka Furue and Hiroki Yoshida and Hiromitsu Hara",

note = "Funding Information: We thank Shizuko Furukawa for secretarial assistance; Fumihiro Mutoh, Shoko Takao, Ritsuko Yoshida, Rie Ogawa, Kimika Nakamura and Takahiro Kaji for technical assistance; S.W. Moris (St Jude Children{\textquoteright}s Research Hospital), S. Akira (Osaka University) and S. Jung (The Weizmann Institute of Science) for BCL10−/−, MyD88−/− and CD11c-DTR Tg mice, respectively; Yayoi Sato, Kenji Shimizu and Takayuki Uematsu for discussions. This study was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of the Japanese Government (24117714 and 22021034; H.H.), the Takeda Science Foundation (H.H.) and the Waksman Foundation of Japan Inc. (H.Y.). There are no conflicts of interest in connection of this work.",

year = "2014",

month = may,

day = "7",

doi = "10.1038/ncomms4755",

language = "English",

volume = "5",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

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T1 - An ITAM-Syk-CARD9 signalling axis triggers contact hypersensitivity by stimulating il-1 production in dendritic cells

AU - Yasukawa, Shinsuke

AU - Miyazaki, Yoshiyuki

AU - Yoshii, Chika

AU - Nakaya, Mako

AU - Ozaki, Naoko

AU - Toda, Shuji

AU - Kuroda, Etsushi

AU - Ishibashi, Ken Ichi

AU - Yasuda, Tomoharu

AU - Natsuaki, Yohei

AU - Mi-Ichi, Fumika

AU - Iizasa, Eíichi

AU - Nakahara, Takeshi

AU - Yamazaki, Masanori

AU - Kabashima, Kenji

AU - Iwakura, Yoichiro

AU - Takai, Toshiyuki

AU - Saito, Takashi

AU - Kurosaki, Tomohiro

AU - Malissen, Bernard

AU - Ohno, Naohito

AU - Furue, Masutaka

AU - Yoshida, Hiroki

AU - Hara, Hiromitsu

N1 - Funding Information: We thank Shizuko Furukawa for secretarial assistance; Fumihiro Mutoh, Shoko Takao, Ritsuko Yoshida, Rie Ogawa, Kimika Nakamura and Takahiro Kaji for technical assistance; S.W. Moris (St Jude Children’s Research Hospital), S. Akira (Osaka University) and S. Jung (The Weizmann Institute of Science) for BCL10−/−, MyD88−/− and CD11c-DTR Tg mice, respectively; Yayoi Sato, Kenji Shimizu and Takayuki Uematsu for discussions. This study was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of the Japanese Government (24117714 and 22021034; H.H.), the Takeda Science Foundation (H.H.) and the Waksman Foundation of Japan Inc. (H.Y.). There are no conflicts of interest in connection of this work.

PY - 2014/5/7

Y1 - 2014/5/7

N2 - 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-1Î± /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.

AB - 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-1Î± /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.

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JO - Nature Communications

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

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