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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
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    Cited by:

    1. 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.
    2. 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.

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