IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v7y2016i1d10.1038_ncomms12993.html
   My bibliography  Save this article

ICER is requisite for Th17 differentiation

Author

Listed:
  • Nobuya Yoshida

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Denis Comte

    (Beth Israel Deaconess Medical Center, Harvard Medical School
    Centre Hospitalier Universitaire Vaudois)

  • Masayuki Mizui

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Kotaro Otomo

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Florencia Rosetti

    (Center for Excellence in Vascular Biology, Brigham and Women’s Hospital, Harvard Medical School)

  • Tanya N. Mayadas

    (Center for Excellence in Vascular Biology, Brigham and Women’s Hospital, Harvard Medical School)

  • José C. Crispín

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Sean J. Bradley

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Tomohiro Koga

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Michihito Kono

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Maria P. Karampetsou

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Vasileios C. Kyttaris

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Klaus Tenbrock

    (RWTH University of Aachen)

  • George C. Tsokos

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

Abstract

Inducible cAMP early repressor (ICER) has been described as a transcriptional repressor isoform of the cAMP response element modulator (CREM). Here we report that ICER is predominantly expressed in Th17 cells through the IL-6–STAT3 pathway and binds to the Il17a promoter, where it facilitates the accumulation of the canonical enhancer RORγt. In vitro differentiation from naive ICER/CREM-deficient CD4+ T cells to Th17 cells is impaired but can be rescued by forced overexpression of ICER. Consistent with a role of Th17 cells in autoimmune and inflammatory diseases, ICER/CREM-deficient B6.lpr mice are protected from developing autoimmunity. Similarly, both anti-glomerular basement membrane-induced glomerulonephritis and experimental encephalomyelitis are attenuated in ICER/CREM-deficient mice compared with their ICER/CREM-sufficient littermates. Importantly, we find ICER overexpressed in CD4+ T cells from patients with systemic lupus erythematosus. Collectively, our findings identify a unique role for ICER, which affects both organ-specific and systemic autoimmunity in a Th17-dependent manner.

Suggested Citation

  • Nobuya Yoshida & Denis Comte & Masayuki Mizui & Kotaro Otomo & Florencia Rosetti & Tanya N. Mayadas & José C. Crispín & Sean J. Bradley & Tomohiro Koga & Michihito Kono & Maria P. Karampetsou & Vasile, 2016. "ICER is requisite for Th17 differentiation," Nature Communications, Nature, vol. 7(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12993
    DOI: 10.1038/ncomms12993
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms12993
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms12993?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
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Kuniyuki Aso & Michihito Kono & Masatoshi Kanda & Yuki Kudo & Kodai Sakiyama & Ryo Hisada & Kohei Karino & Yusho Ueda & Daigo Nakazawa & Yuichiro Fujieda & Masaru Kato & Olga Amengual & Tatsuya Atsumi, 2023. "Itaconate ameliorates autoimmunity by modulating T cell imbalance via metabolic and epigenetic reprogramming," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    2. Marc Scherlinger & Hao Li & Wenliang Pan & Wei Li & Kohei Karino & Theodoros Vichos & Afroditi Boulougoura & Nobuya Yoshida & Maria G. Tsokos & George C. Tsokos, 2024. "CaMK4 controls follicular helper T cell expansion and function during normal and autoimmune T-dependent B cell responses," Nature Communications, Nature, vol. 15(1), pages 1-11, December.

    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:7:y:2016:i:1:d:10.1038_ncomms12993. 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.