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

DOI PDF Web Site PubMed 被引用文献22件 参考文献52件 オープンアクセス

書誌事項

公開日
2017-01-09
資源種別
journal article
権利情報
  • https://creativecommons.org/licenses/by/4.0
  • https://creativecommons.org/licenses/by/4.0
DOI
  • 10.1038/ncomms13946
公開者
Springer Science and Business Media LLC

説明

<jats:title>Abstract</jats:title><jats:p>Mutations of<jats:italic>DOCK8</jats:italic>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<jats:sup>+</jats:sup>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<jats:sup>+</jats:sup>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<jats:italic>Il31</jats:italic>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<jats:sup>+</jats:sup>T cells.</jats:p>

収録刊行物

  • Nature Communications

    Nature Communications 8 (1), 13946-, 2017-01-09

    Springer Science and Business Media LLC

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