{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T22:58:47Z","timestamp":1773788327952,"version":"3.50.1"},"reference-count":74,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,2,26]],"date-time":"2024-02-26T00:00:00Z","timestamp":1708905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Chang Gung Memorial Hospital","award":["CMRPG 5I0072"],"award-info":[{"award-number":["CMRPG 5I0072"]}]},{"name":"Chang Gung Memorial Hospital","award":["CMRPG 5H0022"],"award-info":[{"award-number":["CMRPG 5H0022"]}]},{"name":"Chang Gung Memorial Hospital","award":["CMRPG 3J1422"],"award-info":[{"award-number":["CMRPG 3J1422"]}]},{"name":"Chang Gung Memorial Hospital","award":["MOST 109-2314-B-182-068-MY3"],"award-info":[{"award-number":["MOST 109-2314-B-182-068-MY3"]}]},{"name":"Ministry of Science and Technology, Taiwan","award":["CMRPG 5I0072"],"award-info":[{"award-number":["CMRPG 5I0072"]}]},{"name":"Ministry of Science and Technology, Taiwan","award":["CMRPG 5H0022"],"award-info":[{"award-number":["CMRPG 5H0022"]}]},{"name":"Ministry of Science and Technology, Taiwan","award":["CMRPG 3J1422"],"award-info":[{"award-number":["CMRPG 3J1422"]}]},{"name":"Ministry of Science and Technology, Taiwan","award":["MOST 109-2314-B-182-068-MY3"],"award-info":[{"award-number":["MOST 109-2314-B-182-068-MY3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Co-inhibitory receptors (Co-IRs) are essential in controlling the progression of immunopathology in rheumatoid arthritis (RA) by limiting T cell activation. The objective of this investigation was to determine the phenotypic expression of Co-IR T cells and to assess the levels of serum soluble PD-1, PDL-2, and TIM3 in Taiwanese RA patients. Methods: Co-IRs T cells were immunophenotyped employing multicolor flow cytometry, and ELISA was utilized for measuring soluble PD-1, PDL-2, and TIM3. Correlations have been detected across the percentage of T cells expressing Co-IRs (MFI) and different indicators in the blood, including ESR, high-sensitivity CRP (hsCRP), 28 joint disease activity scores (DAS28), and soluble PD-1\/PDL-2\/TIM3. Results: In RA patients, we recognized elevated levels of PD-1 (CD279), CTLA-4, and TIGIT in CD4+ T cells; TIGIT, HLA-DR, TIM3, and LAG3 in CD8+ T cells; and CD8+CD279+TIM3+, CD8+HLA-DR+CD38+ T cells. The following tests were revealed to be correlated with hsCRP: CD4\/CD279 MFI, CD4\/CD279%, CD4\/TIM3%, CD8\/TIM3%, CD8\/TIM3 MFI, CD8\/LAG3%, and CD8+HLA-DR+CD38+%. CD8\/LAG3 and CD8\/TIM3 MFIs are linked to ESR. DAS28-ESR and DAS28-CRP exhibited relationships with CD4\/CD127 MFI, CD8\/CD279%, and CD8\/CD127 MFI, respectively. CD4+CD279+TIM3+% was correlated with DAS28-ESR (p = 0.0084, N = 46), DAS28-CRP (p = 0.007, N = 47), and hsCRP (p = 0.002, N = 56), respectively. In the serum of patients with RA, levels of soluble PD-1, PDL-2, and Tim3 were extremely elevated. CD4+ TIM3+% (p = 0.0089, N = 46) and CD8+ TIM3+% (p = 0.0305, N = 46) were correlated with sTIM3 levels; sPD1 levels were correlated with CD4+CD279+% (p &lt; 0.0001, N = 31) and CD3+CD279+% (p = 0.0084, N = 30). Conclusions: Co-IR expressions on CD4+ and CD8+ T cells, as well as soluble PD-1, PDL-2, and TIM3 levels, could function as indicators of disease activity and potentially play crucial roles in the pathogenesis of RA.<\/jats:p>","DOI":"10.3390\/cells13050403","type":"journal-article","created":{"date-parts":[[2024,2,26]],"date-time":"2024-02-26T07:51:39Z","timestamp":1708933899000},"page":"403","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Comprehensive Co-Inhibitory Receptor (Co-IR) Expression on T Cells and Soluble Proteins in Rheumatoid Arthritis"],"prefix":"10.3390","volume":"13","author":[{"given":"Chin-Man","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Rehabilitation, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan 33302, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yeong-Jian","family":"Jan Wu","sequence":"additional","affiliation":[{"name":"Division of Allergy, Immunology and Rheumatology, Department of Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, No. 5, Fu-Shin St. Kwei-Shan, Taoyuan 33305, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li-Yu","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Allergy, Immunology and Rheumatology, Department of Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, No. 5, Fu-Shin St. Kwei-Shan, Taoyuan 33305, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian-Wen","family":"Zheng","sequence":"additional","affiliation":[{"name":"Division of Allergy, Immunology and Rheumatology, Department of Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, No. 5, Fu-Shin St. Kwei-Shan, Taoyuan 33305, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji-Yih","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Allergy, Immunology and Rheumatology, Department of Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, No. 5, Fu-Shin St. Kwei-Shan, Taoyuan 33305, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2328","DOI":"10.1016\/S0140-6736(17)31472-1","article-title":"Pathogenetic insights from the treatment of rheumatoid arthritis","volume":"389","author":"McInnes","year":"2017","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"v3","DOI":"10.1093\/rheumatology\/kes113","article-title":"Understanding the dynamics: Pathways involved in the pathogenesis of rheumatoid arthritis","volume":"51","author":"Choy","year":"2012","journal-title":"Rheumatology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"384","DOI":"10.3389\/fimmu.2015.00384","article-title":"T Cell Migration in Rheumatoid Arthritis","volume":"6","author":"Mellado","year":"2015","journal-title":"Front. 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