IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v11y2020i1d10.1038_s41467-020-16363-w.html
   My bibliography  Save this article

TGF-β signaling in Th17 cells promotes IL-22 production and colitis-associated colon cancer

Author

Listed:
  • Laura Garcia Perez

    (University Medical Center Hamburg-Eppendorf)

  • Jan Kempski

    (University Medical Center Hamburg-Eppendorf)

  • Heather M. McGee

    (Salk Institute for Biological Studies)

  • Penelope Pelzcar

    (University Medical Center Hamburg-Eppendorf)

  • Theodora Agalioti

    (University Medical Center Hamburg-Eppendorf)

  • Anastasios Giannou

    (University Medical Center Hamburg-Eppendorf)

  • Leonie Konczalla

    (University Medical Center Hamburg-Eppendorf)

  • Leonie Brockmann

    (Columbia University)

  • Ramez Wahib

    (University Medical Center Hamburg-Eppendorf)

  • Hao Xu

    (Yale University)

  • Maria Carolina Amezcua Vesely

    (Yale University)

  • Shiwa Soukou

    (University Medical Center Hamburg-Eppendorf)

  • Babett Steglich

    (University Medical Center Hamburg-Eppendorf
    University Medical Center Hamburg-Eppendorf)

  • Tanja Bedke

    (University Medical Center Hamburg-Eppendorf)

  • Carolin Manthey

    (University Medical Center Hamburg-Eppendorf)

  • Oliver Seiz

    (University Medical Center Hamburg-Eppendorf)

  • Björn-Philipp Diercks

    (University Medical Center Hamburg-Eppendorf)

  • Stylianos Gnafakis

    (Laboratory of Innate Immunity, Department of Microbiology, Infectious Diseases and Immunology, Charité - Universitätsmedizin Berlin
    Berlin Institute of Health (BIH), Anna-Louisa-Karsch Strasse 2
    Mucosal and Developmental Immunology, Deutsches Rheuma-Forschungszentrum)

  • Andreas H. Guse

    (University Medical Center Hamburg-Eppendorf)

  • Daniel Perez

    (University Medical Center Hamburg-Eppendorf)

  • Jakob R. Izbicki

    (University Medical Center Hamburg-Eppendorf)

  • Nicola Gagliani

    (University Medical Center Hamburg-Eppendorf
    University Medical Center Hamburg-Eppendorf
    Karolinska Institute and University Hospital)

  • Richard A. Flavell

    (Yale University
    Yale University)

  • Samuel Huber

    (University Medical Center Hamburg-Eppendorf)

Abstract

IL-22 has dual functions during tumorigenesis. Short term IL-22 production protects against genotoxic stress, whereas uncontrolled IL-22 activity promotes tumor growth; therefore, tight regulation of IL-22 is essential. TGF-β1 promotes the differentiation of Th17 cells, which are known to be a major source of IL-22, but the effect of TGF-β signaling on the production of IL-22 in CD4+ T cells is controversial. Here we show an increased presence of IL-17+IL-22+ cells and TGF-β1 in colorectal cancer compared to normal adjacent tissue, whereas the frequency of IL-22 single producing cells is not changed. Accordingly, TGF-β signaling in CD4+ T cells (specifically Th17 cells) promotes the emergence of IL-22-producing Th17 cells and thereby tumorigenesis in mice. IL-22 single producing T cells, however, are not dependent on TGF-β signaling. We show that TGF-β, via AhR induction, and PI3K signaling promotes IL-22 production in Th17 cells.

Suggested Citation

  • Laura Garcia Perez & Jan Kempski & Heather M. McGee & Penelope Pelzcar & Theodora Agalioti & Anastasios Giannou & Leonie Konczalla & Leonie Brockmann & Ramez Wahib & Hao Xu & Maria Carolina Amezcua Ve, 2020. "TGF-β signaling in Th17 cells promotes IL-22 production and colitis-associated colon cancer," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16363-w
    DOI: 10.1038/s41467-020-16363-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-020-16363-w
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-020-16363-w?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:11:y:2020:i:1:d:10.1038_s41467-020-16363-w. 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.