Induction of the IL-1RII decoy receptor by NFAT/FOXP3 Blocks IL-1β-dependent response of Th17 cells
- Seoul National University College of Medicine, Republic of Korea
- Chungnam National University Hospital, Republic of Korea
- Hanyang University College of Natural Sciences, Republic of Korea
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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
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.
Reviewing Editor
- Kiyoshi Takeda, Osaka University, Japan
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.
Version history
- Received: August 6, 2020
- Accepted: January 28, 2021
- Accepted Manuscript published: January 28, 2021 (version 1)
- 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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Induction of the IL-1RII decoy receptor by NFAT/FOXP3 Blocks IL-1β-dependent response of Th17 cells
eLife 10:e61841.
https://doi.org/10.7554/eLife.61841
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