Chen Yan-Juan, Chen Yong, Chen Ping, Jia Yi-Qun, Wang Hua, Hong Xiao-Ping
Department of Rheumatology and Immunology The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital Shenzhen China.
Integrated Chinese and Western Medicine Postdoctoral Research Station Jinan University Guangzhou China.
Clin Transl Immunology. 2024 Sep 27;13(10):e70006. doi: 10.1002/cti2.70006. eCollection 2024.
PD-1 plays a crucial role in the immune dysregulation of rheumatoid arthritis (RA), but the specific characteristics of PD-1CD4 T cells remain unclear and require further investigation.
Circulating PD-1CD4 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-1CD4 T cells. Expression of CCR7, KLF2 and IL32 in PD-1CD4 T cells was validated by flow cytometry.
RA patients showed an elevated proportion of PD-1CD4 T cells in peripheral blood, along with increased plasma sPD-1 levels, which positively correlated with TNF-α and erythrocyte sedimentation rate. Bioinformatic analysis revealed expression on CCR7CD4 T cells in PBMCs, and on both CCR7CD4 T cells and CXCL13CD4 T cells in RA synovium. PD-1 was co-expressed with CCR7, KLF2, and IL32 in peripheral CD4 T cells. In synovium, PD-1CCR7CD4 T cells had higher expression of and , while PD-1CXCL13CD4 T cells showed elevated levels of and . PD-1CD4 T cells in synovium also appeared to interact with B cells and fibroblasts through BTLA and TNFSF signalling pathways.
This study highlights the increased proportion of PD-1CD4 T cells and elevated sPD-1 levels in RA. The transcriptomic profiles and signalling networks of PD-1CD4 T cells offer new insights into their role in RA pathogenesis.
程序性死亡受体1（PD - 1）在类风湿关节炎（RA）的免疫失调中起关键作用，但PD - 1⁺CD4⁺T细胞的具体特征仍不清楚，需要进一步研究。
采用流式细胞术分析RA患者循环中的PD - 1⁺CD4⁺T细胞。使用酶联免疫吸附测定（ELISA）检测血浆中可溶性PD - 1（sPD - 1）水平。从基因表达综合数据库（GEO）和免疫数据库（ImmPort）获取患者外周血单个核细胞（PBMC）和滑膜组织的单细胞RNA序列数据。在R工作室进行生物信息学分析以表征PD - 1⁺CD4⁺T细胞。通过流式细胞术验证PD - 1⁺CD4⁺T细胞中趋化因子受体7（CCR7）、 Kruppel样因子2（KLF2）和白细胞介素32（IL32）的表达。
RA患者外周血中PD - 1⁺CD4⁺T细胞比例升高，同时血浆sPD - 1水平增加，且与肿瘤坏死因子-α（TNF - α）和红细胞沉降率呈正相关。生物信息学分析显示，PBMC中CCR7⁺CD4⁺T细胞以及RA滑膜中CCR7⁺CD4⁺T细胞和CXC趋化因子配体13（CXCL13）⁺CD4⁺T细胞上均有表达。外周CD4⁺T细胞中PD - 1与CCR7、KLF2和IL32共表达。在滑膜中，PD - 1⁺CCR7⁺CD4⁺T细胞中 和 的表达较高，而PD - 1⁺CXCL13⁺CD4⁺T细胞中 和 水平升高。滑膜中的PD - 1⁺CD4⁺T细胞似乎还通过B和T淋巴细胞衰减蛋白（BTLA）和肿瘤坏死因子超家族（TNFSF）信号通路与B细胞和成纤维细胞相互作用。
本研究强调了RA中PD - 1⁺CD4⁺T细胞比例增加和sPD - 1水平升高。PD - 1⁺CD4⁺T细胞的转录组谱和信号网络为其在RA发病机制中的作用提供了新见解。
