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Capicua deficiency induces autoimmunity and promotes follicular helper T cell differentiation via derepression of ETV5

Author

Listed:
  • Sungjun Park

    (Pohang University of Science and Technology)

  • Seungwon Lee

    (Pohang University of Science and Technology)

  • Choong-Gu Lee

    (Academy of Immunology and Microbiology, Institute for Basic Science)

  • Guk Yeol Park

    (Pohang University of Science and Technology)

  • Hyebeen Hong

    (Pohang University of Science and Technology)

  • Jeon-Soo Lee

    (Pohang University of Science and Technology)

  • Young Min Kim

    (Pohang University of Science and Technology)

  • Sung Bae Lee

    (Daegu Gyeongbuk Institute of Science and Technology (DGIST))

  • Daehee Hwang

    (Center for Plant Aging Research, Institute for Basic Science, DGIST)

  • Youn Soo Choi

    (Seoul National University College of Medicine
    Transplantation Research Institute, Seoul National University College of Medicine)

  • John D. Fryer

    (Mayo Clinic)

  • Sin-Hyeog Im

    (Pohang University of Science and Technology
    Pohang University of Science and Technology
    Academy of Immunology and Microbiology, Institute for Basic Science)

  • Seung-Woo Lee

    (Pohang University of Science and Technology
    Pohang University of Science and Technology)

  • Yoontae Lee

    (Pohang University of Science and Technology
    Pohang University of Science and Technology)

Abstract

High-affinity antibody production through the germinal centre (GC) response is a pivotal process in adaptive immunity. Abnormal development of follicular helper T (TFH) cells can induce the GC response to self-antigens, subsequently leading to autoimmunity. Here we show the transcriptional repressor Capicua/CIC maintains peripheral immune tolerance by suppressing aberrant activation of adaptive immunity. CIC deficiency induces excessive development of TFH cells and GC responses in a T-cell-intrinsic manner. ETV5 expression is derepressed in Cic null TFH cells and knockdown of Etv5 suppresses the enhanced TFH cell differentiation in Cic-deficient CD4+ T cells, suggesting that Etv5 is a critical CIC target gene in TFH cell differentiation. Furthermore, we identify Maf as a downstream target of the CIC–ETV5 axis in this process. These data demonstrate that CIC maintains T-cell homeostasis and negatively regulates TFH cell development and autoimmunity.

Suggested Citation

  • Sungjun Park & Seungwon Lee & Choong-Gu Lee & Guk Yeol Park & Hyebeen Hong & Jeon-Soo Lee & Young Min Kim & Sung Bae Lee & Daehee Hwang & Youn Soo Choi & John D. Fryer & Sin-Hyeog Im & Seung-Woo Lee &, 2017. "Capicua deficiency induces autoimmunity and promotes follicular helper T cell differentiation via derepression of ETV5," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms16037
    DOI: 10.1038/ncomms16037
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    Cited by:

    1. Jong Seok Park & Minjung Kang & Han Bit Kim & Hyebeen Hong & Jongeun Lee & Youngkwon Song & Yunjung Hur & Soeun Kim & Tae-Kyung Kim & Yoontae Lee, 2024. "The capicua-ataxin-1-like complex regulates Notch-driven marginal zone B cell development and sepsis progression," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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