Cigarette smoking promotes inflammation in patients with COPD by affecting the polarization and survival of Th/Tregs through up-regulation of muscarinic receptor 3 and 5 expression.
Cigarette smoking promotes inflammation in patients with COPD by affecting the polarization and survival of Th/Tregs through up-regulation of muscarinic receptor 3 and 5 expression.
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吸烟通过上调毒蕈碱受体 3 和 5 的表达，影响 Th/Treg 的极化和存活，从而促进 COPD 患者的炎症
DOI：
10.1371/journal.pone.0112350
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Chen G
中科院分区：
文献类型：
--
作者：
Zhang MQ;Wan Y;Jin Y;Xin JB;Zhang JC;Xiong XZ;Chen L;Chen G
肺中的CD4+ T细胞参与慢性阻塞性肺疾病（COPD）的发病机制，尽管CD4+ T细胞亚群和吸烟对这些细胞的直接影响，特别是MRs的表达尚未得到全面研究。方法首先采用流式细胞术检测健康非吸烟者、SCOPD患者和AECOPD患者的循环CD4+ T细胞亚群。采用RT-PCR进行分化实验，Ki-67/Annexin V抗体检测细胞增殖和凋亡。我们还探讨了CSE对CD4+Th/Tregs的分化和存活的影响，并检测了健康非吸烟者和SCOPD患者中MRs的表达。结果我们发现AECOPD患者循环Th1和Th17细胞百分比增加，而SCOPD患者循环Th2细胞百分比下降。SCOPD和AECOPD患者中Th10细胞的百分比均降低，Tregs细胞的百分比升高。此外，SCOPD患者和AECOPD患者CD4+α-7+ T细胞百分比均降低。然而，仅在AECOPD患者中观察到明显的下降。体外研究还显示MR表达影响T细胞的极化，不同的CD4+ T细胞亚型获得不同的MR表达谱。CSE的加入促进CD4+ T细胞向促炎亚群（Th1和Th17）极化，并通过上调MR3和5的表达影响CD4+ T细胞和Treg细胞的存活，导致CD4+ T细胞亚群失衡。结论：我们的研究结果表明，循环CD4+ T细胞亚群的失衡参与了吸烟者COPD的发病机制。吸烟可能通过MR3和MR5的上调影响Th/Tregs的极化和存活，从而导致这种不平衡。
Background CD4+ T cells in the lung are involved in the pathogenesis of chronic obstructive pulmonary disease (COPD), although CD4+ T cell subsets and the direct effect of smoking on these cells, especially the expression of MRs, have not been comprehensively examined. Methods First, circulating CD4+ T cell subsets in healthy nonsmokers, patients with SCOPD and patients with AECOPD were evaluated by flow cytometry. Then, differentiation experiments were carried out using RT-PCR, and Ki-67/Annexin V antibodies were used to measure proliferation and apoptosis. We also explored the impact of CSE on the differentiation and survival of CD4+Th/Tregs and examined the expression of MRs in healthy nonsmokers and patients with SCOPD. Results We found the percentages of circulating Th1 and Th17 cells were increased in patients with AECOPD, while the percentage of Th2 cells was decreased in patients with SCOPD. The percentages of Th10 cells were decreased in both patients with SCOPD and patients with AECOPD, while the percentages of Tregs were increased. In addition, the percentages of CD4+α-7+ T cells were decreased in patients with SCOPD and patients with AECOPD. However, only the decrease observed in patients with AECOPD was significant. In vitro studies also revealed MR expression affected the polarization of T cells, with different CD4+ T cell subtypes acquiring different MR expression profiles. The addition of CSE facilitated CD4+ T cell polarization towards pro-inflammatory subsets (Th1 and Th17) and affected the survival of CD4+ T cells and Treg cells by up-regulating the expression of MR3 and 5, resulting in an imbalance of CD4+ T cell subsets. Conclusions Our findings suggest an imbalance of circulating CD4+ T cell subsets is involved in COPD pathogenesis in smokers. Cigarette smoking may contribute to this imbalance by affecting the polarization and survival of Th/Tregs through the up-regulation of MR3 and MR5.
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影响因子：
3.7
作者：
Fujihara, Masashi;Nagai, Norihiro;Sussan, Thomas E.;Biswal, Shyam;Handa, James T.
通讯作者：
Handa, James T.
影响因子：
3.3
作者：
De Rosa, MJ;Esandi, MD;Bouzat, C
通讯作者：
Bouzat, C
影响因子：
24.3
作者：
Isajevs, S.;Taivans, I.;Kratovska, A.
通讯作者：
Kratovska, A.
影响因子：
158.5
作者：
GROSS, NJ;SKORODIN, MS
通讯作者：
SKORODIN, MS
影响因子：
3.3
作者：
HellstromLindahl, E;Nordberg, A
通讯作者：
Nordberg, A