Association between inflammatory cytokines and immune–checkpoint molecule in rheumatoid arthritis
<h4>Background</h4> Anti-citrullinated peptide antibodies (ACPA) and inflammatory cytokines play important roles in the development of rheumatoid arthritis (RA). T cell immunoglobulin and mucin–domain containing–3 (TIM–3) is an immune-checkpoint molecule involved in inhibitory signaling....
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2021-01-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8601500/?tool=EBI |
| _version_ | 1818931614728585216 |
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| author | Haruki Matsumoto Yuya Fujita Tomoyuki Asano Naoki Matsuoka Jumpei Temmoku Shuzo Sato Makiko Yashiro–Furuya Kohei Yokose Shuhei Yoshida Eiji Suzuki Toru Yago Hiroshi Watanabe Atsushi Kawakami Kiyoshi Migita |
| author_facet | Haruki Matsumoto Yuya Fujita Tomoyuki Asano Naoki Matsuoka Jumpei Temmoku Shuzo Sato Makiko Yashiro–Furuya Kohei Yokose Shuhei Yoshida Eiji Suzuki Toru Yago Hiroshi Watanabe Atsushi Kawakami Kiyoshi Migita |
| author_sort | Haruki Matsumoto |
| collection | DOAJ |
| description | <h4>Background</h4> Anti-citrullinated peptide antibodies (ACPA) and inflammatory cytokines play important roles in the development of rheumatoid arthritis (RA). T cell immunoglobulin and mucin–domain containing–3 (TIM–3) is an immune-checkpoint molecule involved in inhibitory signaling. Galectin–9 (Gal–9) mediated ligation of TIM–3 induces the amelioration of autoimmune diseases. TIM–3 is expressed in synovial osteoclasts and involved in the rheumatoid bone destruction. The aim of this study was to investigate the relationships between inflammatory cytokines and immune–checkpoint molecules in RA patients. <h4>Methods</h4> Serum levels of interleukin–6 (IL–6), tumor necrosis factor–α (TNF–α), soluble TIM–3 (sTIM–3) and Gal–9 were determined by ELISA. Patients were stratified into two groups based on ACPA titers: low-medium ACPA (ACPA <200 U/mL) and high ACPA (ACPA ≥200 U/mL). Serum levels of cytokines or immune-checkpoint molecules were evaluated between RA patients with low-medium ACPA titers and high ACPA titers. <h4>Results</h4> Elevated serum levels of inflammatory cytokines were correlated with DAS28–ESR in RA patients. Although serum levels of sTIM–3 were elevated in RA patients, significant correlations between sTIM–3 and cytokines (IL–6 or TNF–α) were observed exclusively in RA patients with low-medium ACPA titers (<200 U/mL). Serum levels of IL–6 and TNF–α levels were significantly correlated with elevated Gal–9 levels regardless of ACPA status. A significant correlation between IL–6 and Gal–9 was observed in RA patients without advanced joint damage. Conversely, a significant correlation between TNF–α and Gal–9 was observed in RA patients with advanced joint damage. <h4>Conclusions</h4> Our data indicated that there are positive correlations between circulating inflammatory cytokines and checkpoint molecules in RA patients and these interactions can be modulated by ACPA status or joint damage stage. |
| first_indexed | 2024-12-20T04:19:24Z |
| format | Article |
| id | doaj.art-5146651f887140efad76d4db9c829101 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T04:19:24Z |
| publishDate | 2021-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-5146651f887140efad76d4db9c8291012022-12-21T19:53:40ZengPublic Library of Science (PLoS)PLoS ONE1932-62032021-01-011611Association between inflammatory cytokines and immune–checkpoint molecule in rheumatoid arthritisHaruki MatsumotoYuya FujitaTomoyuki AsanoNaoki MatsuokaJumpei TemmokuShuzo SatoMakiko Yashiro–FuruyaKohei YokoseShuhei YoshidaEiji SuzukiToru YagoHiroshi WatanabeAtsushi KawakamiKiyoshi Migita<h4>Background</h4> Anti-citrullinated peptide antibodies (ACPA) and inflammatory cytokines play important roles in the development of rheumatoid arthritis (RA). T cell immunoglobulin and mucin–domain containing–3 (TIM–3) is an immune-checkpoint molecule involved in inhibitory signaling. Galectin–9 (Gal–9) mediated ligation of TIM–3 induces the amelioration of autoimmune diseases. TIM–3 is expressed in synovial osteoclasts and involved in the rheumatoid bone destruction. The aim of this study was to investigate the relationships between inflammatory cytokines and immune–checkpoint molecules in RA patients. <h4>Methods</h4> Serum levels of interleukin–6 (IL–6), tumor necrosis factor–α (TNF–α), soluble TIM–3 (sTIM–3) and Gal–9 were determined by ELISA. Patients were stratified into two groups based on ACPA titers: low-medium ACPA (ACPA <200 U/mL) and high ACPA (ACPA ≥200 U/mL). Serum levels of cytokines or immune-checkpoint molecules were evaluated between RA patients with low-medium ACPA titers and high ACPA titers. <h4>Results</h4> Elevated serum levels of inflammatory cytokines were correlated with DAS28–ESR in RA patients. Although serum levels of sTIM–3 were elevated in RA patients, significant correlations between sTIM–3 and cytokines (IL–6 or TNF–α) were observed exclusively in RA patients with low-medium ACPA titers (<200 U/mL). Serum levels of IL–6 and TNF–α levels were significantly correlated with elevated Gal–9 levels regardless of ACPA status. A significant correlation between IL–6 and Gal–9 was observed in RA patients without advanced joint damage. Conversely, a significant correlation between TNF–α and Gal–9 was observed in RA patients with advanced joint damage. <h4>Conclusions</h4> Our data indicated that there are positive correlations between circulating inflammatory cytokines and checkpoint molecules in RA patients and these interactions can be modulated by ACPA status or joint damage stage.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8601500/?tool=EBI |
| spellingShingle | Haruki Matsumoto Yuya Fujita Tomoyuki Asano Naoki Matsuoka Jumpei Temmoku Shuzo Sato Makiko Yashiro–Furuya Kohei Yokose Shuhei Yoshida Eiji Suzuki Toru Yago Hiroshi Watanabe Atsushi Kawakami Kiyoshi Migita Association between inflammatory cytokines and immune–checkpoint molecule in rheumatoid arthritis PLoS ONE |
| title | Association between inflammatory cytokines and immune–checkpoint molecule in rheumatoid arthritis |
| title_full | Association between inflammatory cytokines and immune–checkpoint molecule in rheumatoid arthritis |
| title_fullStr | Association between inflammatory cytokines and immune–checkpoint molecule in rheumatoid arthritis |
| title_full_unstemmed | Association between inflammatory cytokines and immune–checkpoint molecule in rheumatoid arthritis |
| title_short | Association between inflammatory cytokines and immune–checkpoint molecule in rheumatoid arthritis |
| title_sort | association between inflammatory cytokines and immune checkpoint molecule in rheumatoid arthritis |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8601500/?tool=EBI |
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