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COPD 不同阶段调节性 T 细胞的表型。

Phenotypes of regulatory T cells in different stages of COPD.

机构信息

Laboratory of Experimental Therapeutics - (LIM20), Department of Clinical Medicine, School of Medicine, University of São Paulo, Brazil.

Laboratory of Dermatology and Immunodeficiencies - LIM56, Department of Dermatology, Tropical Medicine Institute of São Paulo, School of Medicine, University of São Paulo, Brazil.

出版信息

Int Immunopharmacol. 2024 Oct 25;140:112765. doi: 10.1016/j.intimp.2024.112765. Epub 2024 Jul 30.

Abstract

BACKGROUND

Previous studies have shown that failure to control inflammatory processes mediated by regulatory T (Treg) cells contributes to chronic obstructive pulmonary disease (COPD) development and progression. The activity of Treg cells depends on their phenotypic characteristics: resting Treg (rTreg, CD3+CD4+CD25+FOXP3+CD25++CD45RA+) and activated Treg (aTreg, CD3+CD4+CD25+FOXP3+CD25+++CD45RA-) cells exhibit immunosuppressive activity, while cytokine-secreting T cells (FrIII, CD3+CD4+CD25+FOXP3+CD25++CD45RA-) exhibit proinflammatory activity. Previous findings have shown an increased density of cytokine-secreting T cells in COPD patients experiencing exacerbation. However, the methods for evaluating COPD under stable conditions are lacking.

AIM

To evaluate Treg cell phenotypes in patients with different stages of COPD under stable conditions.

METHODS

Peripheral blood mononuclear cells (PBMCs) were isolated from non-obstructed smokers and ex-smokers (NOS group, n = 19) and COPD patients at different stages (COPD I-II group, n = 25; COPD III-IV group, n = 25). The phenotypic characteristics of Treg cells and Th17 cells and their respective intracellular cytokines were analyzed by flow cytometry.

RESULTS

Both obstructed groups showed an increase in the proportion of rTregs, while the COPD III-IV group showed additional increases in total Treg and Th17 cells and in IL-10+ cells. There was an increase in proinflammatory mediators (CD3+CD4+IL-17+ cells; CD3+CD4+RORγt+ cells) in the COPD I-II group. In contrast, the NOS group demonstrated high proportions of proinflammatory Treg cells and proinflammatory CD8+ T cells (CD3+CD8+IL-17+).

CONCLUSION

Despite the increase in both total Treg cells and the rTreg phenotype from the early stages of COPD, there was a decrease in cells expressing IL-10, suggesting a failure in controlling the inflammatory process. These events precede the progression of the inflammatory process mediated by Th17 cells.

摘要

背景

既往研究表明,调节性 T(Treg)细胞介导的炎症过程失控是导致慢性阻塞性肺疾病(COPD)发生和进展的原因之一。Treg 细胞的活性取决于其表型特征:静息 Treg(rTreg,CD3+CD4+CD25+FOXP3+CD25++CD45RA+)和激活的 Treg(aTreg,CD3+CD4+CD25+FOXP3+CD25+++CD45RA-)细胞具有免疫抑制活性,而分泌细胞因子的 T 细胞(FrIII,CD3+CD4+CD25+FOXP3+CD25++CD45RA-)则具有促炎活性。既往研究显示,在 COPD 加重患者中,分泌细胞因子的 T 细胞密度增加。然而,在稳定状态下评估 COPD 的方法尚缺乏。

目的

评估稳定状态下不同阶段 COPD 患者 Treg 细胞表型。

方法

从非阻塞性吸烟者和戒烟者(NOS 组,n=19)和不同阶段的 COPD 患者(COPD I-II 组,n=25;COPD III-IV 组,n=25)中分离外周血单核细胞(PBMC)。采用流式细胞术分析 Treg 细胞和 Th17 细胞的表型特征及其各自的细胞内细胞因子。

结果

两组阻塞性组的 rTreg 比例均增加,而 COPD III-IV 组的总 Treg 和 Th17 细胞以及 IL-10+细胞比例进一步增加。COPD I-II 组促炎介质(CD3+CD4+IL-17+细胞;CD3+CD4+RORγt+细胞)增加。相比之下,NOS 组表现出高比例的促炎 Treg 细胞和促炎 CD8+T 细胞(CD3+CD8+IL-17+)。

结论

尽管从 COPD 的早期阶段开始,总 Treg 细胞和 rTreg 表型均增加,但表达 IL-10 的细胞减少,提示炎症过程失控。这些事件发生在 Th17 细胞介导的炎症过程进展之前。

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