1. Immunology and Inflammation
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Induction of the IL-1RII decoy receptor by NFAT/FOXP3 Blocks IL-1β-dependent response of Th17 cells

  1. Dong Hyun Kim
  2. Hee Young Kim
  3. Sunjung Cho
  4. Su-Jin Yoo
  5. Won-Ju Kim
  6. Hye Ran Yeon
  7. Kyungho Choi
  8. Je-Min Choi
  9. Seong Wook Kang
  10. Won-Woo Lee  Is a corresponding author
  1. Seoul National University College of Medicine, Republic of Korea
  2. Chungnam National University Hospital, Republic of Korea
  3. Hanyang University College of Natural Sciences, Republic of Korea
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Cite this article as: eLife 2021;10:e61841 doi: 10.7554/eLife.61841

Abstract

Derived from a common precursor cell, the balance between Th17 and Treg cells must be maintained within immune system to prevent autoimmune diseases. IL-1β-mediated IL-1 receptor (IL-1R) signaling is essential for Th17-cell biology. Fine-tuning of IL-1R signaling is controlled by two receptors, IL-1RI and IL-RII, IL-1R accessory protein, and IL-1R antagonist. We demonstrate that the decoy receptor, IL-1RII, is important for regulating IL-17 responses in TCR-stimulated CD4+ T cells expressing functional IL-1RI via limiting IL-1β responsiveness. IL-1RII expression is regulated by NFAT via its interaction with Foxp3. The NFAT/FOXP3 complex binds to the IL-1RII promoter and is critical for its transcription. Additionally, IL-1RII expression is dysregulated in CD4+ T cells from patients with rheumatoid arthritis. Thus, differential expression of IL-1Rs on activated CD4+ T cells defines unique immunological features and a novel molecular mechanism underlies IL-1RII expression. These findings shed light on the modulatory effects of IL-1RII on Th17 responses.

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All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Dong Hyun Kim

    Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  2. Hee Young Kim

    Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  3. Sunjung Cho

    Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  4. Su-Jin Yoo

    Internal Medicine, Chungnam National University Hospital, Daejeon, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  5. Won-Ju Kim

    Life Science,, Hanyang University College of Natural Sciences, Seoul, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  6. Hye Ran Yeon

    Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  7. Kyungho Choi

    Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  8. Je-Min Choi

    Life Science,, Hanyang University College of Natural Sciences, Seoul, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  9. Seong Wook Kang

    Internal Medicine, Chungnam National University Hospital, Daejeon, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  10. Won-Woo Lee

    Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea
    For correspondence
    wonwoolee@snu.ac.kr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5347-9591

Funding

National Research Foundation of Korea (2013R1A1A2012522)

  • Won-Woo Lee

National Research Foundation of Korea (2018R1A2B2006310)

  • Won-Woo Lee

Seoul National University Hospital (0320180220: 2018-1293)

  • Won-Woo Lee

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: The study protocols were approved by the institutional review board (IRB) of Seoul National University Hospital and Chungnam National University Hospital (IRB No.1109- 055-378, 1306-002-491, and 1403-049-564 for Seoul National University College of Medicine/Seoul National University Hospital and IRB No.2012-01-024 for Chungnam National University Hospital). Peripheral blood of RA patients and healthy controls (HCs) was drawn after obtaining written, informed consent.

Reviewing Editor

  1. Kiyoshi Takeda, Osaka University, Japan

Publication history

  1. Received: August 6, 2020
  2. Accepted: January 28, 2021
  3. Accepted Manuscript published: January 28, 2021 (version 1)
  4. Version of Record published: February 9, 2021 (version 2)

Copyright

© 2021, Kim et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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