组蛋白去乙酰化酶在香烟烟雾暴露下Treg细胞中的表达及作用的研究

Chronic obstructive pulmonary disease (COPD) is induced by T lymphocyte-dependent inflammation and autoimmunity caused by smoking. Our previous studies have shown that the lack of regulatory T cells (Tregs) suppressive function in a cigarette-induced emphysema rat model contributes to the progression of emphysema. Currently, there are relatively few studies that have addressed the mechanism underlying how cigarette smoking leads to the lack of Tregs suppressive functions. Based on preliminary work, this study investigated expressions of histone deacetylases in Tregs due to smoking exposure. We evaluated the effects of abnormal histone deacetylases on the function and phenotype of Tregs induced by cigarette smoke and the related intracellular signal transduction mechanisms to investigate the mechanism underlying the smoking-induced impairment of Tregs suppressive functions. This study provided a theoretical basis to further elucidate the mechanism of cellular immunity in COPD and to aid in the search for effective clinical therapeutic targets and new prevention approaches for COPD. It has certain innovation and feasibility.

慢性阻塞性肺疾病（chronic obstructive pulmonary disease, COPD）是一种吸烟所诱发的由T淋巴细胞参与的炎症反应和自身免疫性所引起的疾病。我们前期研究显示吸烟诱导的肺气肿大鼠调节性T细胞 (regulatory T cells, Treg)的功能缺陷与肺气肿形成密切相关，但对于香烟如何导致Treg细胞功能缺陷机制目前研究尚少。本课题在前期研究的基础上，以Treg 细胞为研究对象，观察香烟烟雾暴露下Treg细胞中组蛋白去乙酰化酶的表达，研究香烟烟雾暴露下组蛋白去乙酰化酶的异常对Treg细胞功能和亚型的影响及其相关的细胞内信号转导机制，以探讨吸烟导致Treg细胞功能失衡的机制，对进一步阐明COPD的细胞免疫学发生机制，并为临床上寻找COPD新的有效治疗靶点和防治方法提供理论依据。具有一定创新性和可行性。

慢性阻塞性肺疾病（chronic obstructive pulmonary disease, COPD）是一种吸烟所诱发的由T淋巴细胞参与的炎症反应和自身免疫性所引起的疾病。本课题在前期研究的基础上，以Treg 细胞为研究对象，应用香烟提取物和组蛋白去乙酰化酶抑制剂（TSA）为工具药，观察香烟烟雾暴露下Treg细胞中组蛋白去乙酰化酶的表达和作用。我们发现在香烟烟雾暴露下，Treg细胞中HDAC2、HDAC7、HDAC9的表达下降，同时伴有Treg细胞增殖能力增加，Treg细胞亚型中记忆型Treg细胞、效应型Treg细胞比例升高而幼稚型Treg细胞比例下降，功能性标志物Foxp3、CTLA-4表达增高和CD4+CD25+INF-γ+细胞和CD4+CD25+IL-17+细胞表达比率增高，使用TSA抑制组蛋白去乙酰化酶后，上述变化进一步增强，提示香烟烟雾暴露下Treg细胞中存在有组蛋白去乙酰化酶表达的异常，同时伴有具有抑制功能Treg细胞亚型数量增加、Treg免疫抑制功能增强和Treg细胞诱导CD4T细胞向Th1、Th17分化能力增强，而这一变化与Treg细胞中组蛋白去乙酰化酶表达异常有关。我们的研究对于阐明吸烟导致Treg细胞功能失衡的机制，并进一步探讨COPD的细胞免疫学发生机制具有重要意义。