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