Comprehensive Co-Inhibitory Receptor (Co-IR) Expression on T Cells and Soluble Proteins in Rheumatoid Arthritis

Chin Man Wang; Yeong Jian Jan Wu; Li Yu Huang; Jian Wen Zheng; Ji Yih Chen

doi:10.3390/cells13050403

Comprehensive Co-Inhibitory Receptor (Co-IR) Expression on T Cells and Soluble Proteins in Rheumatoid Arthritis

Chin Man Wang, Yeong Jian Jan Wu, Li Yu Huang, Jian Wen Zheng, Ji Yih Chen^*

^*Corresponding author for this work

School of Medicine

Chang Gung University

Research output: Contribution to journal › Journal Article › peer-review

1 Scopus citations

Abstract

UNLABELLED: 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 < 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.

Original language	English
Article number	403
Journal	Cells
Volume	13
Issue number	5
DOIs	https://doi.org/10.3390/cells13050403
State	Published - 26 02 2024

Bibliographical note

Publisher Copyright:
© 2024 by the authors.

Keywords

co-inhibitory receptors
disease activity
RA
T cell
HLA-DR Antigens
Humans
Receptors, Immunologic
Programmed Cell Death 1 Receptor
C-Reactive Protein/metabolism
Hepatitis A Virus Cellular Receptor 2
Arthritis, Rheumatoid/pathology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.3390/cells13050403

Cite this

@article{b75e9c26ece84cf3b41fa6dad317535d,

title = "Comprehensive Co-Inhibitory Receptor (Co-IR) Expression on T Cells and Soluble Proteins in Rheumatoid Arthritis",

abstract = "UNLABELLED: 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 < 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.",

keywords = "co-inhibitory receptors, disease activity, RA, T cell, HLA-DR Antigens, Humans, Receptors, Immunologic, Programmed Cell Death 1 Receptor, C-Reactive Protein/metabolism, Hepatitis A Virus Cellular Receptor 2, Arthritis, Rheumatoid/pathology",

author = "Wang, {Chin Man} and {Jan Wu}, {Yeong Jian} and Huang, {Li Yu} and Zheng, {Jian Wen} and Chen, {Ji Yih}",

note = "Publisher Copyright: {\textcopyright} 2024 by the authors.",

year = "2024",

month = feb,

day = "26",

doi = "10.3390/cells13050403",

language = "英语",

volume = "13",

journal = "Cells",

issn = "2073-4409",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "5",

}

TY - JOUR

T1 - Comprehensive Co-Inhibitory Receptor (Co-IR) Expression on T Cells and Soluble Proteins in Rheumatoid Arthritis

AU - Wang, Chin Man

AU - Jan Wu, Yeong Jian

AU - Huang, Li Yu

AU - Zheng, Jian Wen

AU - Chen, Ji Yih

PY - 2024/2/26

Y1 - 2024/2/26

N2 - UNLABELLED: 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 < 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.

AB - UNLABELLED: 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 < 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.

KW - co-inhibitory receptors

KW - disease activity

KW - RA

KW - T cell

KW - HLA-DR Antigens

KW - Humans

KW - Receptors, Immunologic

KW - Programmed Cell Death 1 Receptor

KW - C-Reactive Protein/metabolism

KW - Hepatitis A Virus Cellular Receptor 2

KW - Arthritis, Rheumatoid/pathology

UR - http://www.scopus.com/inward/record.url?scp=85187887827&partnerID=8YFLogxK

U2 - 10.3390/cells13050403

DO - 10.3390/cells13050403

M3 - 文章

C2 - 38474367

AN - SCOPUS:85187887827

SN - 2073-4409

VL - 13

JO - Cells

JF - Cells

IS - 5

M1 - 403

ER -

Comprehensive Co-Inhibitory Receptor (Co-IR) Expression on T Cells and Soluble Proteins in Rheumatoid Arthritis

Abstract

Bibliographical note

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this