Wang, C.-M.; Jan Wu, Y.-J.; Huang, L.-Y.; Zheng, J.-W.; Chen, J.-Y. Comprehensive Co-Inhibitory Receptor (Co-IR) Expression on T Cells and Soluble Proteins in Rheumatoid Arthritis. Cells2024, 13, 403.
Wang, C.-M.; Jan Wu, Y.-J.; Huang, L.-Y.; Zheng, J.-W.; Chen, J.-Y. Comprehensive Co-Inhibitory Receptor (Co-IR) Expression on T Cells and Soluble Proteins in Rheumatoid Arthritis. Cells 2024, 13, 403.
Wang, C.-M.; Jan Wu, Y.-J.; Huang, L.-Y.; Zheng, J.-W.; Chen, J.-Y. Comprehensive Co-Inhibitory Receptor (Co-IR) Expression on T Cells and Soluble Proteins in Rheumatoid Arthritis. Cells2024, 13, 403.
Wang, C.-M.; Jan Wu, Y.-J.; Huang, L.-Y.; Zheng, J.-W.; Chen, J.-Y. Comprehensive Co-Inhibitory Receptor (Co-IR) Expression on T Cells and Soluble Proteins in Rheumatoid Arthritis. Cells 2024, 13, 403.
Abstract
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-IRs T cells and to assess the levels of serum soluble PD-1, PDL-2, and Tim3 in Taiwanese RA patients. 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. In RA patients, we recognized elevated levels of PD-1 (CD279), CTLA-4, and TIGIT on CD4+ T cells; TIGIT, HLA-DR, TIM3, and LAG3 on CD8+ T cells; and CD8+CD279+TIM3+, CD8+HLA-DR+CD38+ T cells. The following tests proved 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<0.0001, N=31) and CD3+CD279+% (p=0.0084, N=30). Co-IRs 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, in accordance to our findings.
Keywords
Rheumatoid arthritis; T cell; Co-inhibitory receptors; disease activity
Subject
Medicine and Pharmacology, Immunology and Allergy
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
