Characteristics of PD-1⁺CD4⁺ T cells in peripheral blood and synovium of rheumatoid arthritis patients

Chen, Yan-juan1,2; Chen, Yong3; Chen, Ping4; Jia, Yi-qun5; Wang, Hua6; Hong, Xiao-ping7

2024

10.1002/cti2.70006

CLINICAL & TRANSLATIONAL IMMUNOLOGY   影响因子和分区

2050-0068

Objectives. PD-1 plays a crucial role in the immune dysregulation of rheumatoid arthritis (RA), but the specific characteristics of PD-1(+)CD4(+) T cells remain unclear and require further investigation. Methods. Circulating PD-1(+)CD4(+) T cells from RA patients were analysed using flow cytometry. Plasma levels of soluble PD-1 (sPD-1) were measured using enzyme-linked immunosorbent assay (ELISA). Single-cell RNA sequence data from peripheral blood mononuclear cells (PBMCs) and synovial tissue of patients were obtained from the GEO and the ImmPort databases. Bioinformatics analyses were performed in the R studio to characterise PD-1(+)CD4(+) T cells. Expression of CCR7, KLF2 and IL32 in PD-1(+)CD4(+) T cells was validated by flow cytometry. Results. RA patients showed an elevated proportion of PD-1(+)CD4(+) T cells in peripheral blood, along with increased plasma sPD-1 levels, which positively correlated with TNF-alpha and erythrocyte sedimentation rate. Bioinformatic analysis revealed PD-1 expression on CCR7(+)CD4(+) T cells in PBMCs, and on both CCR7(+)CD4(+) T cells and CXCL13(+)CD4(+) T cells in RA synovium. PD-1 was co-expressed with CCR7, KLF2, and IL32 in peripheral CD4(+) T cells. In synovium, PD-1(+)CCR7(+)CD4(+) T cells had higher expression of TNF and LCP2, while PD-1(+)CXCL13(+)CD4(+) T cells showed elevated levels of ARID5A and DUSP2. PD-1(+)CD4(+) T cells in synovium also appeared to interact with B cells and fibroblasts through BTLA and TNFSF signalling pathways. Conclusion. This study highlights the increased proportion of PD-1(+)CD4(+) T cells and elevated sPD-1 levels in RA. The transcriptomic profiles and signalling networks of PD-1(+)CD4(+) T cells offer new insights into their role in RA pathogenesis.

CD4(+) T cells PD-1 rheumatoid arthritis single-cell RNA-seq soluble PD-1

SCI

英语

通讯

Shenzhen, China[SZSM202111006] ; Sanming Project of Medicine in Shenzhen[SZXK011] ; Shenzhen Key Medical Discipline Construction Fund[82302030]

Immunology

Immunology

WOS:001320926300001

WILEY

Web of Science

1.Jinan Univ, Shenzhen Peoples Hosp, Clin Med Coll 2, Dept Rheumatol & Immunol, Shenzhen, Peoples R China
2.Jinan Univ, Integrated Chinese & Western Med Postdoctoral Res, Guangzhou, Peoples R China
3.Zunyi Med Univ, Affiliated Hosp, Dept Rheumatol & Immunol, Zunyi, Peoples R China
4.Shenzhen Peoples Hosp, Dept Rheumatol & Immunol, Shenzhen, Peoples R China
5.Jinan Univ, Shenzhen Peoples Hosp, Clin Med Coll 2, Stomatol Ctr, Shenzhen, Peoples R China
6.Southern Univ Sci & Technol, Jinan Univ, Afiliated Hosp 1, Shenzhen Peoples Hosp,Clin Med Coll 2,Dept Orthopa, 1017 Dongmen North Rd, Shenzhen 518020, Peoples R China
7.Southern Univ Sci & Technol, Jinan Univ, Affiliated Hosp 1, Shenzhen Peoples Hosp,Clin Med Coll 2,Dept Rheumat, 1017 Dongmen North Rd, Shenzhen 518020, Peoples R China

Chen, Yan-juan,Chen, Yong,Chen, Ping,et al. Characteristics of PD-1⁺CD4⁺ T cells in peripheral blood and synovium of rheumatoid arthritis patients[J]. CLINICAL & TRANSLATIONAL IMMUNOLOGY,2024,13(10).

Chen, Yan-juan,Chen, Yong,Chen, Ping,Jia, Yi-qun,Wang, Hua,&Hong, Xiao-ping.(2024).Characteristics of PD-1⁺CD4⁺ T cells in peripheral blood and synovium of rheumatoid arthritis patients.CLINICAL & TRANSLATIONAL IMMUNOLOGY,13(10).

Chen, Yan-juan,et al."Characteristics of PD-1⁺CD4⁺ T cells in peripheral blood and synovium of rheumatoid arthritis patients".CLINICAL & TRANSLATIONAL IMMUNOLOGY 13.10(2024).