The transcription factor EPAS1 links DOCK8 deficiency to atopic skin inflammation via IL-31 induction

Kazuhiko Yamamura, Takehito Uruno, Akira Shiraishi, Yoshihiko Tanaka, Miho Ushijima, Takeshi Nakahara, Mayuki Watanabe, Makiko Kido-Nakahara, Ikuya Tsuge, Masutaka Furue, Yoshinori Fukui

研究成果: ジャーナルへの寄稿記事

19 引用 (Scopus)

抄録

Mutations of DOCK8 in humans cause a combined immunodeficiency characterized by atopic dermatitis with high serum IgE levels. However, the molecular link between DOCK8 deficiency and atopic skin inflammation is unknown. Here we show that CD4+ T cells from DOCK8-deficient mice produce large amounts of IL-31, a major pruritogen associated with atopic dermatitis. IL-31 induction critically depends on the transcription factor EPAS1, and its conditional deletion in CD4+ T cells abrogates skin disease development in DOCK8-deficient mice. Although EPAS1 is known to form a complex with aryl hydrocarbon receptor nuclear translocator (ARNT) and control hypoxic responses, EPAS1-mediated Il31 promoter activation is independent of ARNT, but in collaboration with SP1. On the other hand, we find that DOCK8 is an adaptor and negative regulator of nuclear translocation of EPAS1. Thus, EPAS1 links DOCK8 deficiency to atopic skin inflammation via IL-31 induction in CD4+ T cells.

元の言語英語
記事番号13946
ジャーナルNature communications
8
DOI
出版物ステータス出版済み - 1 9 2017

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T-cells
Aryl Hydrocarbon Receptor Nuclear Translocator
dermatitis
Skin
induction
Transcription Factors
Atopic Dermatitis
Inflammation
T-Lymphocytes
mice
hydrocarbons
deletion
regulators
mutations
Skin Diseases
serums
Immunoglobulin E
Chemical activation
activation
Mutation

All Science Journal Classification (ASJC) codes

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

これを引用

The transcription factor EPAS1 links DOCK8 deficiency to atopic skin inflammation via IL-31 induction. / Yamamura, Kazuhiko; Uruno, Takehito; Shiraishi, Akira; Tanaka, Yoshihiko; Ushijima, Miho; Nakahara, Takeshi; Watanabe, Mayuki; Kido-Nakahara, Makiko; Tsuge, Ikuya; Furue, Masutaka; Fukui, Yoshinori.

:: Nature communications, 巻 8, 13946, 09.01.2017.

研究成果: ジャーナルへの寄稿記事

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abstract = "Mutations of DOCK8 in humans cause a combined immunodeficiency characterized by atopic dermatitis with high serum IgE levels. However, the molecular link between DOCK8 deficiency and atopic skin inflammation is unknown. Here we show that CD4+ T cells from DOCK8-deficient mice produce large amounts of IL-31, a major pruritogen associated with atopic dermatitis. IL-31 induction critically depends on the transcription factor EPAS1, and its conditional deletion in CD4+ T cells abrogates skin disease development in DOCK8-deficient mice. Although EPAS1 is known to form a complex with aryl hydrocarbon receptor nuclear translocator (ARNT) and control hypoxic responses, EPAS1-mediated Il31 promoter activation is independent of ARNT, but in collaboration with SP1. On the other hand, we find that DOCK8 is an adaptor and negative regulator of nuclear translocation of EPAS1. Thus, EPAS1 links DOCK8 deficiency to atopic skin inflammation via IL-31 induction in CD4+ T cells.",
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AU - Ushijima, Miho

AU - Nakahara, Takeshi

AU - Watanabe, Mayuki

AU - Kido-Nakahara, Makiko

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AU - Furue, Masutaka

AU - Fukui, Yoshinori

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