Laboratory of Autoimmunity and Inflammation (LAI), Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea
Hee Young Kim
Laboratory of Autoimmunity and Inflammation (LAI), Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea; Cancer Research Institute and Institute of Infectious Diseases, Seoul National University College of Medicine, Seoul, Republic of Korea
Sunjung Cho
Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea
Su-Jin Yoo
Department of Internal Medicine, Chungnam National University School of Medicine, 282 Munhwa-ro, Jung-gu, Daejeon, Republic of Korea
Won-Ju Kim
Department of Life Science, College of Natural Sciences and Research Institute for Natural Sciences, Hanyang University, Seoul, Republic of Korea
Hye Ran Yeon
Department of Biochemistry and Molecular Biology, Department of Biomedical Sciences, and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
Kyungho Choi
Department of Biochemistry and Molecular Biology, Department of Biomedical Sciences, and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
Je-Min Choi
Department of Life Science, College of Natural Sciences and Research Institute for Natural Sciences, Hanyang University, Seoul, Republic of Korea
Seong Wook Kang
Department of Internal Medicine, Chungnam National University School of Medicine, 282 Munhwa-ro, Jung-gu, Daejeon, Republic of Korea
Laboratory of Autoimmunity and Inflammation (LAI), Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea; Cancer Research Institute and Institute of Infectious Diseases, Seoul National University College of Medicine, Seoul, Republic of Korea; Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine; Seoul National University Hospital Biomedical Research Institute, Seoul, Republic of Korea
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.
