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CXCL11影响狼疮患者调节性T细胞的功能(英文)

陈鹏宇^1,2,3, 郭华^1,3, 王雨楠^1,2,3, 康杭^2,4, 杨能杰^1,2,3, 戴越潇^1,3,5, 顾志峰^1,2,3, 夏云飞^1,2,3,*

¹南通大学附属医院风湿免疫科，南通 226001；²南通大学，南通 226001；³南通大学附属医院临床医学研究中心，南通 226001；⁴南通大学生殖医学研究所，南通 226001；⁵大连医科大学，大连 116000

摘要

系统性红斑狼疮(systemic lupus erythematosus, SLE)是一种慢性自身免疫性疾病，调节性T细胞(regulatory T cell,Treg)的缺陷在打破SLE患者的免疫耐受中起着关键作用。本研究旨在探讨SLE 患者Treg 细胞功能受损的原因。收集56例SLE患者和33名健康志愿者的外周血，检测Treg 细胞占CD4⁺ T细胞的比例和血浆细胞因子水平。从健康人外周血单个核细胞中分离Treg 细胞和初始CD4⁺ T细胞，并在不同条件下培养。采用流式细胞术、RT-qPCR、蛋白免疫印迹和钙信号转导实验检测Treg的表型和信号转导机制。结果显示，SLE患者外周血CD4⁺CD25⁺Foxp3⁺和CD4⁺Foxp3⁺ Treg细胞比例降低，细胞因子CXCL11在SLE患者血浆中升高。CXCL11 的表达与CD4⁺CD25⁺Foxp3⁺ Treg 细胞比例呈负相关，与狼疮严重程度呈正相关。CXCL11 损伤Treg 细胞免疫抑制功能，抑制Treg细胞分化。因此，我们揭示了一个新的SLE病理途径，即CXCL11阻碍Treg细胞的免疫抑制功能。

关键词： 系统性红斑狼疮; 调节性T细胞; CXCL11

CXCL11 impairs the function of regulatory T cells in lupus patients

CHEN Peng-Yu^1,2,3, GUO Hua^1,3, WANG Yu-Nan^1,2,3, KANG Hang^2,4, YANG Neng-Jie^1,2,3, DAI Yue-Xiao^1,3,5, GU Zhi-Feng^1,2,3, XIA Yun-Fei^1,2,3,*

¹Department of Rheumatology, Affiliated Hospital of Nantong University, Nantong 226001, China；²Nantong University, Nantong 226001, China；³Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, China；⁴Institute of Reproductive Medicine, Nantong University, Nantong 226001, China；⁵Dalian Medical University, Dalian 116000, China

Abstract

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. Defects in the regulatory T cells (Treg cells) play a key role in breaking immune tolerance in SLE patients. This study investigates the causes of impaired Treg cell function in SLE patients. Peripheral blood from 56 SLE patients and 33 healthy donors was used to assess Treg cell proportions among CD4+ T cells and plasma cytokine levels. Treg cells and naïve CD4+ T cells from healthy individuals were isolated, cultured under various conditions, and analyzed for phenotype and signal transduction mechanisms using flow cytometry, RT-qPCR, Western blotting, and calcium signaling assays. In SLE patients, the proportion of CD4+CD25+Foxp3+ and CD4+Foxp3+ Treg cells decreased. Plasma CXCL11 levels were elevated in lupus patients. CXCL11 expression inversely correlated with Treg cell proportions and positively correlated with disease severity. CXCL11 impaired immune function and inhibited Treg cell differentiation. We present a novel pathological pathway in SLE, wherein CXCL11 impedes the immunosuppressive functions of Treg cells.

Key words: systemic lupus erythematosus; regulatory T cell; CXCL11

收稿日期：　　录用日期：

通讯作者：夏云飞　　E-mail:

DOI: 10.13294/j.aps.2025.0097

引用本文：

陈鹏宇, 郭华, 王雨楠, 康杭, 杨能杰, 戴越潇, 顾志峰, 夏云飞. CXCL11影响狼疮患者调节性T细胞的功能(英文)[J]. 生理学报 2025; 77 (6): 1133-1147.

CHEN Peng-Yu, GUO Hua, WANG Yu-Nan, KANG Hang, YANG Neng-Jie, DAI Yue-Xiao, GU Zhi-Feng, XIA Yun-Fei. CXCL11 impairs the function of regulatory T cells in lupus patients. Acta Physiol Sin 2025; 77 (6): 1133-1147