IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v8y2017i1d10.1038_ncomms13946.html
   My bibliography  Save this article

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

Author

Listed:
  • Kazuhiko Yamamura

    (Medical Institute of Bioregulation, Kyushu University
    Graduate School of Medical Sciences, Kyushu University)

  • Takehito Uruno

    (Medical Institute of Bioregulation, Kyushu University
    Research Centre for Advanced Immunology, Kyushu University)

  • Akira Shiraishi

    (Medical Institute of Bioregulation, Kyushu University)

  • Yoshihiko Tanaka

    (Section of Infection Biology, Fukuoka Dental College)

  • Miho Ushijima

    (Medical Institute of Bioregulation, Kyushu University)

  • Takeshi Nakahara

    (Graduate School of Medical Sciences, Kyushu University)

  • Mayuki Watanabe

    (Medical Institute of Bioregulation, Kyushu University)

  • Makiko Kido-Nakahara

    (Graduate School of Medical Sciences, Kyushu University)

  • Ikuya Tsuge

    (School of Medicine, Fujita Health University)

  • Masutaka Furue

    (Graduate School of Medical Sciences, Kyushu University)

  • Yoshinori Fukui

    (Medical Institute of Bioregulation, Kyushu University
    Research Centre for Advanced Immunology, Kyushu University)

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.

Suggested Citation

  • Kazuhiko Yamamura & Takehito Uruno & Akira Shiraishi & Yoshihiko Tanaka & Miho Ushijima & Takeshi Nakahara & Mayuki Watanabe & Makiko Kido-Nakahara & Ikuya Tsuge & Masutaka Furue & Yoshinori Fukui, 2017. "The transcription factor EPAS1 links DOCK8 deficiency to atopic skin inflammation via IL-31 induction," Nature Communications, Nature, vol. 8(1), pages 1-13, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms13946
    DOI: 10.1038/ncomms13946
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms13946
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms13946?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms13946. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.