{"title":"调节性T细胞在慢性阻塞性肺疾病中的作用","authors":"Meghashree Sampath, Geetanjali Bade, Randeep Guleria, Anant Mohan, Sudip Sen, Anjana Talwar","doi":"10.1155/pm/5048054","DOIUrl":null,"url":null,"abstract":"<p><p><b>Background:</b> Chronic obstructive pulmonary disease (COPD) is a progressive lung disorder characterized by poorly reversible airway obstruction. COPD being an inflammatory disorder has been proposed to have an imbalance between proinflammatory and anti-inflammatory factors. Regulatory T cells (Tregs) being a negative regulator of immune response have been observed to play an important role in other inflammatory diseases as well as animal models of inflammation. <b>Objective</b>: This study is aimed at assessing the suppressive functions of circulatory Tregs and examining the inductive capacity of naive CD4+ T cells to generate induced Tregs. <b>Methods:</b> The study was conducted in 20 COPD patients (smokers <i>n</i> = 10; reformed smokers <i>n</i> = 10) and 20 age-matched healthy controls (smokers <i>n</i> = 10; nonsmokers <i>n</i> = 10). Peripheral blood mononuclear cells were isolated from blood using Ficoll density gradient separation. The suppressive functions were evaluated by assessing the proliferation of T responder cells (CD4+CD25-) in the presence of circulatory Tregs (CD4+CD25+) under polyclonal stimulation. In addition, cytokine-mediated suppression was assessed in the culture supernatants of the suppression assay. Inductive capacity was assessed by stimulating naive CD4+ T cells to generate iTregs in the presence of anti-CD3, IL-2, and TGF-<i>β</i>1. <b>Results:</b> The percent suppression of T responder cells by Tregs was significantly lower in COPD smokers (<i>p</i> = 0.03) and COPD reformed smokers (<i>p</i> = 0.04) as compared to control smokers. On the assessment of cytokine-mediated suppression, significantly reduced IL-2 in COPD S as compared to COPD RS (<i>p</i> < 0.05) and reduced IL-10 and TGFß1 in COPD S as compared to CNS (<i>p</i> < 0.05) and CS (<i>p</i> < 0.05) was observed in the culture supernatants of suppression assay. In addition, a significantly higher frequency of iTregs with phenotype CD4+CD25+CD45RA+CD127- was observed in COPD S as compared to COPD RS (<i>p</i> < 0.01). <b>Discussion:</b> Characteristics changes were observed in patients with COPD. The compromised Tregs function, despite the increase in systemic inflammation, suggests a potential role of these cells in the pathogenesis of the disease.</p>","PeriodicalId":46434,"journal":{"name":"Pulmonary Medicine","volume":"2025 ","pages":"5048054"},"PeriodicalIF":2.0000,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11991774/pdf/","citationCount":"0","resultStr":"{\"title\":\"Role of Regulatory T Cells in Chronic Obstructive Pulmonary Disease.\",\"authors\":\"Meghashree Sampath, Geetanjali Bade, Randeep Guleria, Anant Mohan, Sudip Sen, Anjana Talwar\",\"doi\":\"10.1155/pm/5048054\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><b>Background:</b> Chronic obstructive pulmonary disease (COPD) is a progressive lung disorder characterized by poorly reversible airway obstruction. COPD being an inflammatory disorder has been proposed to have an imbalance between proinflammatory and anti-inflammatory factors. Regulatory T cells (Tregs) being a negative regulator of immune response have been observed to play an important role in other inflammatory diseases as well as animal models of inflammation. <b>Objective</b>: This study is aimed at assessing the suppressive functions of circulatory Tregs and examining the inductive capacity of naive CD4+ T cells to generate induced Tregs. <b>Methods:</b> The study was conducted in 20 COPD patients (smokers <i>n</i> = 10; reformed smokers <i>n</i> = 10) and 20 age-matched healthy controls (smokers <i>n</i> = 10; nonsmokers <i>n</i> = 10). Peripheral blood mononuclear cells were isolated from blood using Ficoll density gradient separation. The suppressive functions were evaluated by assessing the proliferation of T responder cells (CD4+CD25-) in the presence of circulatory Tregs (CD4+CD25+) under polyclonal stimulation. In addition, cytokine-mediated suppression was assessed in the culture supernatants of the suppression assay. Inductive capacity was assessed by stimulating naive CD4+ T cells to generate iTregs in the presence of anti-CD3, IL-2, and TGF-<i>β</i>1. <b>Results:</b> The percent suppression of T responder cells by Tregs was significantly lower in COPD smokers (<i>p</i> = 0.03) and COPD reformed smokers (<i>p</i> = 0.04) as compared to control smokers. On the assessment of cytokine-mediated suppression, significantly reduced IL-2 in COPD S as compared to COPD RS (<i>p</i> < 0.05) and reduced IL-10 and TGFß1 in COPD S as compared to CNS (<i>p</i> < 0.05) and CS (<i>p</i> < 0.05) was observed in the culture supernatants of suppression assay. In addition, a significantly higher frequency of iTregs with phenotype CD4+CD25+CD45RA+CD127- was observed in COPD S as compared to COPD RS (<i>p</i> < 0.01). <b>Discussion:</b> Characteristics changes were observed in patients with COPD. The compromised Tregs function, despite the increase in systemic inflammation, suggests a potential role of these cells in the pathogenesis of the disease.</p>\",\"PeriodicalId\":46434,\"journal\":{\"name\":\"Pulmonary Medicine\",\"volume\":\"2025 \",\"pages\":\"5048054\"},\"PeriodicalIF\":2.0000,\"publicationDate\":\"2025-03-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11991774/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pulmonary Medicine\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1155/pm/5048054\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q3\",\"JCRName\":\"RESPIRATORY SYSTEM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pulmonary Medicine","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1155/pm/5048054","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"RESPIRATORY SYSTEM","Score":null,"Total":0}
Role of Regulatory T Cells in Chronic Obstructive Pulmonary Disease.
Background: Chronic obstructive pulmonary disease (COPD) is a progressive lung disorder characterized by poorly reversible airway obstruction. COPD being an inflammatory disorder has been proposed to have an imbalance between proinflammatory and anti-inflammatory factors. Regulatory T cells (Tregs) being a negative regulator of immune response have been observed to play an important role in other inflammatory diseases as well as animal models of inflammation. Objective: This study is aimed at assessing the suppressive functions of circulatory Tregs and examining the inductive capacity of naive CD4+ T cells to generate induced Tregs. Methods: The study was conducted in 20 COPD patients (smokers n = 10; reformed smokers n = 10) and 20 age-matched healthy controls (smokers n = 10; nonsmokers n = 10). Peripheral blood mononuclear cells were isolated from blood using Ficoll density gradient separation. The suppressive functions were evaluated by assessing the proliferation of T responder cells (CD4+CD25-) in the presence of circulatory Tregs (CD4+CD25+) under polyclonal stimulation. In addition, cytokine-mediated suppression was assessed in the culture supernatants of the suppression assay. Inductive capacity was assessed by stimulating naive CD4+ T cells to generate iTregs in the presence of anti-CD3, IL-2, and TGF-β1. Results: The percent suppression of T responder cells by Tregs was significantly lower in COPD smokers (p = 0.03) and COPD reformed smokers (p = 0.04) as compared to control smokers. On the assessment of cytokine-mediated suppression, significantly reduced IL-2 in COPD S as compared to COPD RS (p < 0.05) and reduced IL-10 and TGFß1 in COPD S as compared to CNS (p < 0.05) and CS (p < 0.05) was observed in the culture supernatants of suppression assay. In addition, a significantly higher frequency of iTregs with phenotype CD4+CD25+CD45RA+CD127- was observed in COPD S as compared to COPD RS (p < 0.01). Discussion: Characteristics changes were observed in patients with COPD. The compromised Tregs function, despite the increase in systemic inflammation, suggests a potential role of these cells in the pathogenesis of the disease.