Th17细胞和Treg细胞与某些疾病关系的研究进展

初始CD4+T细胞受到外来抗原刺激后,经过增殖并分化为各种效应T细胞。在IL-12和IFN-γ的诱导下分化为Th1细胞,产生IFN-γ,促进机体细胞免疫,从而发挥抗感染、抗肿瘤作用;在IL-4诱导下分化为Th2细胞,分泌IL-4、IL-5和IL-13,     

Th17和Treg细胞在肝细胞癌发生发展中作用的研究进展

原发性肝癌是较常见的恶性肿瘤,其中90%为肝细胞癌,恶性程度高,难以早期诊断,且复发率高,预后极差。具有免疫抑制作用的调节性T细胞(Treg)和具有促炎作用的辅助性T细胞17(Th17)是CD4~+T细胞的两个亚群,两者关系密切并可在特定条件下相互转化,在维持机体免疫平衡过程中发挥着重要作用。近年来免疫学方法治疗肝细胞癌受到广泛重视。越来越多的研究发现,Treg细胞和Th17细胞参与了肝细胞癌的发生发展。该文就Th17细胞和Treg细胞在肝细胞癌发生发展中作用的研究进展作一综述。     

Th17/Treg细胞在原发性胆汁性肝硬化发病中的作用研究进展

原发性胆汁性肝硬化(PBC)属于一种病因未明的自身免疫性疾病。Th17细胞及Treg细胞是CD4+T细胞的两个亚群,分别起着抑制、促进炎症反应的作用,它们在分化和功能上相互抑制。PBC作为肝脏特异性的自身免疫性疾病,诸多研究提示Th17和Treg细胞数量及相关细胞因子在PBC患者中较健康者有差别,但其具体机制仍不清楚。近年来,它们在PBC发病中的变化越来越成为研究的热点。本文重点介绍Treg细胞和Th17细胞的研究现状及其在PBC发病机制中的作用。     

microRNA-21与大鼠肝癌微环境中Th17细胞和Treg细胞表达的相关性

目的研究miRNA(miR)-21与大鼠肝癌微环境中Treg/Th17比值的相关性。方法使用二乙基亚硝胺构建大鼠肝癌模型,检测肝癌大鼠外周血中Treg细胞和Th17细胞的含量,并检测外周血中miR-21的表达含量,分析miR-21含量与Treg/Th17比值的相关性。结果肝癌大鼠外周血中Th17细胞占总的CD4+T细胞含量的5.319%,较对照组增加;同时,Treg细胞占比约为9.472%,较对照组增加;Treg/Th17的比值在模型组大鼠中为1.781,在正常组中为1.478;miR-21在肝癌大鼠外周血中含量增加,并且与Treg/Th17的比值正相关。结论 miR-21的表达水平与Treg/Th17的比值具有正相关性。     

参麦注射液对支气管哮喘患者外周血Th17/Treg细胞的影响

目的 探讨参麦注射液对支气管哮喘(简称哮喘)患者外周血Th17/Treg细胞的影响及其意义.方法 选取山西医科大学第一医院呼吸科急性发作期、缓解期哮喘患者各25例,选取山西医科大学第一医院体检中心肺功能正常、激发或者舒张试验阴性的健康人25例作为对照组,分别使用1640培养液及参麦注射液进行干预处理.抽取晨起空腹静脉血5 ml,运用流式细胞仪对各组外周血Th17细胞、Treg细胞分别占CD4+的比例及Th17/Trcg细胞的比值进行比较,同时检测血清中IL-10因子的水平.结果 ①各组间干预前CD4+ Th17细胞/CD4+T细胞、CD4+ Th17细胞/CD4+ Treg细胞的比值,急性发作期组(3.05±1.27、1.49±1.78)高于缓解期组(2.38±0.93、0.61±0.24)及对照组(1.19±0.39、0.30±1.14),差异有统计学意义(P＜0.05),缓解期高于对照组,差异有统计学意义(P＜0.05);CD4+Treg细胞/CD4+T细胞的比值,对照组(5.20±3.26)高于缓解期组(3.99±0.90)及急性发作期组(2.76±0.93),差异有统计学意义,(P＜0.05),缓解期组高于急性发作期组,差异有统计学意义(P ＜0.05).血清中IL-10因子的水平,对照组(5,28±1.31)高于缓解期组(4.46±0.83)及急性发作期组(3.90±0.64),差异有统计学意义(P＜0.05),缓解期组高于急性发作期组,差异有统计学意义(P ＜0.05).②同一组间CD4+ Th17细胞/CD4+T细胞、CD4+Th17细胞/CD4+ Treg细胞的比值,干预前高于干预后,差异有统计学意义(P＜0.05).CD4+ Treg细胞/CD4+T细胞的比值,干预后高于干预前,差异有统计学意义(P＜0.05).血清中IL-10因子水平,干预后高于干预前,差异有统计学意义(P ＜0.05).结论 哮喘患者外周血中存在Th17/Treg细胞失衡,参麦注射液可以改善哮喘患者的Th17/Treg细胞失衡.     

抗结核治疗对肺结核患者Th17/Treg的影响

目的分析抗结核治疗前后肺结核患者外周血(CD3+CD4+IL-17+)辅助性T细胞17(Th17)和(CD4+CD25+Foxp3+)调节性T细胞(Treg)平衡状态的变化及其临床意义。方法收集本院2014年10月至2015年5月感染科收治的肺结核患者80例,选择30例健康体检者作为对照组。流式细胞术检测患者抗结核药物治疗前、治疗6个月以及对照组的外周血Th17细胞和Treg细胞的表达,ELISA检测外周血中IL-17A的表达。结果流式结果显示,治疗前肺结核患者外周血Th17细胞,Treg细胞表达率为分别为(1.18±0.74)%、(7.68±0.92)%,均明显低于健康体检者((3.95±1.17)%,(4.17±1.12)%,P0.05);治疗6个月后肺结核患者外周血Th17细胞,Treg细胞表达率分别为(2.98±1.42)%,(5.26±0.72)%,均明显高于治疗前、但仍显著低于健康体检者(P0.05)。治疗前肺结核患者Th17/Treg为0.15±0.21,明显低于健康体检者(0.95±0.45,P0.05);治疗6个月后肺结核患者Th17/Treg为0.56±0.39,明显高于治疗前、但仍显著低于健康体检者(P0.05)。ELISA检测结果显示,治疗6个月后肺结核患者外周血IL-17A表达水平为39.06±5.83 pg/m L,明显高于治疗前、但仍显著低于健康体检者(P0.05)。结论结核分枝杆菌可破坏肺结核患者机体Th17/Treg平衡,抗结核治疗可缓解患者外周血Th17/Treg失衡状态。     

抗病毒治疗对慢性丙型肝炎患者Treg/Th17细胞比例变化的影响

目的 了解抗病毒治疗对慢性丙型肝炎患者调节性T细胞(Treg) /Th17细胞比例变化的影响.方法 32例慢性丙型肝炎患者进行聚乙二醇干扰素α-2a联合利巴韦林治疗,20例健康人作为对照.在抗病毒治疗前和随访24周时,采用流式细胞仪检测患者外周血Treg和Th17细胞频率,ELISA法检测患者IL-17的水平,观察Treg/Th17细胞比例变化与患者获得持续性病毒学应答(SVR)的关系.统计学处理采用t检验.结果 抗病毒治疗前患者外周血中Th 17、Treg细胞频率和Treg/Th17比例明显高于对照组[(4.58±0.86)％与(2.48±0.60)％,t=2.399,P＜0.05;(8.58±2.20)％与(4.70±1.30)％,t=7.990,P＜0.01;(1.82±0.40)与(1.60±0.35),t=2.088,P＜0.05].抗病毒治疗后Th 17、Treg细胞频率和Treg/Th17比例分别为(5.35±0.79)％、(6.46±1.29)％、(1.25±0.21).获得SVR患者Th17细胞频率为(6.27±1.15)％,明显高于未获得SVR的(4.05±0.82)％(t=10.103,P＜0.01).获得SVR患者Treg细胞频率和Treg/Th17比例为(4.90±1.39)％、(0.80±0.15),明显低于未获得SVR的(7.42±1.95)％、(1.83±0.42)(t=5.718,8.752,P＜0.01).获得SVR患者IL-17水平为(143.5±31.2)pg/mL,明显高于未获得SVR患者组的(121.4±30.1 )pg/mL(t=2.028,P＜0.05).结论 慢性丙型肝炎患者Treg/Th 17细胞比例高于对照组,抗病毒治疗后Treg/Th17细胞比例下降,获得SVR患者下降更为明显.     

肝衰竭患者外周血Th17/Treg比率测定的价值及其与短期转归的关系

目的探讨肝衰竭患者外周血Th17/Treg比率的检测价值及其与短期转归的关系。方法选取我院2016年5月—2018年5月收治的肝衰竭患者60例,将其作为肝衰竭组,选取同期收治的60例健康体检者作为对照组。两组均于入院当日采血检测外周血Th17、Treg细胞表达情况,并计算二者比值,绘制ROC曲线分析其对肝衰竭的预测价值,获得曲线下面积、最佳截断值以及相应的敏感度、特异度。根据患者6个月内的生存、死亡情况,分成生存组、死亡组,比较两组Th17、Treg细胞表达及Th17/Treg比率,绘制ROC曲线分析其对患者预后的预测价值。结果肝衰竭组Th17细胞、Th17/Treg水平高于对照组,Treg细胞低于对照组,组间比较差异有统计学意义(P0.05)。Th17、Treg细胞及Th17/Treg预测肝衰竭的曲线下面积分别为0.669、0.696、0.710。Th17细胞4.71%、Treg细胞2.98%、Th17/Treg2.40时,肝衰竭患病风险增加。经过6个月随访,有14例死亡,占23.33%,46例生存,占76.67%。生存组Th17细胞、Th17/Treg水平低于死亡组,Treg细胞高于死亡组(P0.05)。Th17、Treg细胞及Th17/Treg预测肝衰竭预后的曲线下面积分别为0.681、0.670、0.754。Th17细胞6.625%、Treg细胞1.859%、Th17/Treg3.045时,肝衰竭患者死亡风险增加。结论与健康者相比,肝衰竭患者的Th17细胞、Th17/Treg水平上调,Treg细胞水平下调,且Th17/Treg比率对预测肝衰竭及患者预后具有较高价值。     

Th17、Treg细胞及其细胞因子变化在特发性肺动脉高压患者中的监测作用

目的分析特发性肺动脉高压(IPAH)患者外周血Th17、Treg细胞及其细胞因子的变化,探讨其在IPAH中的作用。方法以2013年3月-2015年9月本院收治的特发性肺动脉高压患者28例为研究对象,以同期收治的慢性支气管炎患者54例为对照(其中慢性支气管炎合并肺动脉高压者24例,单纯慢性支气管炎患者30例),测定各组外周血Th17和Treg细胞比例和细胞因子。结果 IPAH组和(慢支+PAH)组外周血Th17细胞比例均高于慢支组,而IPAH组和(慢支+PAH)组外周血Th17细胞比例差异无统计学意义;IPAH组和(慢支+PAH)组外周血Treg细胞比例低于慢支组,IPAH组低于(慢支+PAH)组(P0.05);IPAH组和(慢支+PAH)组外周血IL-17水平均高于慢支组,IPAH组高于(慢支+PAH)组(P0.05);IPAH组和(慢支+PAH)组外周血IL-10水平均低于慢支组,IPAH组低于(慢支+PAH)组(P0.05)。IPAH组外周血IL-17水平与肺动脉压力呈正相关(P0.01);IL-10水平与肺动脉压力呈负相关(P0.01)。结论Th17/Treg失衡及其细胞因子变化在特发性肺动脉高压的发生发展中起着重要作用。     

溃疡性结肠炎患者外周血Th17/Treg免疫平衡的研究

目的研究溃疡性结肠炎（UC）患者外周血Th17细胞（CD4＋IL-17＋T细胞）与Treg细胞（CD4^＋CD25^＋T细胞）数量以及相关细胞因子的表达水平,分析Th17／Treg细胞免疫平衡在UC发病机制中的作用。方法收集UC患者（UC组）和健康体检者（对照组）的外周肝素抗凝静脉血,分离纯化T淋巴细胞。分别以PE-CD4与FTTC—CD25单抗,PE-CD4与FITC—IL-17的单抗作双色流式细胞术,分析溃疡性结肠炎患者外周血Th17、Treg细胞的百分率,ELISA法检测血清中相关细胞因子IL-17和TGF—β1的水平。结果与对照组比较,溃疡性结肠炎患者外周血Th17细胞百分率升高,Treg细胞的百分率显著下降,Th17／Treg比值升高（P〈0．05）,血清中细胞因子IL-17升高、TGF-β1降低,并且IL-17／TGF-β1比值升高。结论溃疡性结肠炎患者外周血存在细胞免疫功能失调;Th17／Treg细胞数量与免疫平衡状态发生改变,T淋巴细胞耐受机制的破坏可能与溃疡性结肠炎的发病机制有关。     

Assessment of Th17/Treg cells and Th cytokines in an improved immune thrombocytopenia mouse model

Objectives: The improved passive immune thrombocytopenia (ITP) mouse model has been extensively utilized for the study of ITP. However, how closely this model matches the human inflammation state and immune background is unclear. Our study aimed to explore the profile of Th cytokines and Th17/Treg cells in the model.

Methods: We induced the ITP mouse model by dose-escalation injection of MWReg30. The serum levels of cytokines (IFN-γ, IL-2, IL-4, IL-10, IL-17A, and TGF-β1) were measured by enzyme-linked immunosorbent assay and the frequency of Th17 and Treg cells was measured by flow cytometry. The mRNA expression of Foxp3 and RORrt was measured by real-time PCR.

Results: The serum levels of cytokines IFN-γ, TGF-β1, IL-4, and IL-10 were significantly lower in ITP mice. The secretion of serum proinflammatory cytokines IL-2 and IL-17A and the percentage of Th17 cells showed no statistically significant increase. In ITP mice the frequency of Treg cells and mRNA expression of Foxp3 was significantly lower in splenocytes.

Conclusion: Our data suggest that the improved passive ITP mouse model does not mimic the autoimmune inflammatory process of human ITP. Compared with human ITP, this model has a similar change in frequency of Treg cells, which may directly or indirectly result from antibody-mediated platelet destruction due to attenuated release of TGF-β.     

Treg和Th17细胞在寄生虫感染和卫生假说中的免疫调节

寄生虫感染在发展中国家仍然是一个严重威胁人类健康、影响社会经济发展的公共卫生问题。近年来,随着分子生物学和免疫学等研究进展,人们对寄生虫感染的免疫防御反应及免疫病理机制有了更多认识。CD4~+T细胞在机体免疫防御及免疫调节中发挥着非常重要的作用。传统上认为CD4~+T细胞在体内外可分化成Th1、Th2两大细胞亚群,它们产生不同的细胞因子,发挥不同功能。后来又发现了两种新的CD4~+T细胞亚群,即Th17细胞和调节性T(Treg)细胞。它们具有与传统的Th1、Th2细胞完全不同的、独立的分化和调节机制。已有大量研究证实,Treg和Th17细胞在寄生虫病的抗虫免疫及免疫病理机制中发挥着重要作用。此外,Th17和Treg细胞在寄生虫感染所诱导的卫生假说中的作用越来越受到重视。本文根据当前国内外有关Treg和Th17细胞分化及功能的研究进展,对Treg和Th17细胞在寄生虫感染及卫生假说中的作用作一简要综述。     

Extracellular pyrophosphate is reduced in aortic interstitial valve cells acquiring a calcifying profile: Implications for aortic valve calcification

Objectives: Pyrophosphate (PPi) is a potent inhibitor of ectopic mineralization but its role during aortic valve calcification is not known. Methods: Anti-calcific effect of PPi was investigated by using an in vitro model of serum-driven calcification of collagen sponges and decellularized porcine aortic valve leaflets. Bovine interstitial valve cells (VIC), seeded either within the collagen matrices or in transwell chambers, were used to test cellular ability to inhibit serum-induced calcification. PPi metabolism was investigated in clonal VIC harboring different calcifying potential. Results: In a cell-free system, high serum levels induced a dose-dependent calcification of type I collagen matrices which was prevented by PPi and ATP supplementation. Blockade of serum-driven calcification by PPi and ATP was also observed when using decellularized porcine aortic valve leaflets. A similar anti-calcific effect was also seen for bovine VIC, either statically seeded into the collagen matrices or co-cultured by using a transwell system. However, when we performed co-culture experiments by using clonal VIC harboring different calcifying potential, we observed that the subset of cells acquiring a pro-calcific profile lost the ability to protect the collagen from serum-driven calcification. Pro-calcific differentiation of the clonal VIC was accompanied by increase in ALP along with significant reduction in NPP activity and ATP/PPi extracellular accumulation. These changes were not observed in the clonal subtype with lower propensity towards calcification. Conclusions: We showed that PPi and ATP are potent inhibitors of serum-driven calcification of collagen matrix and that their extracellular accumulation is reduced in calcifying VIC.     

Th17/Treg在支气管哮喘发病机制中的作用及研究进展

Th17/Treg的提出突破了经典理论Th1/Th2失衡的局限性,IL-17、IL-10在支气管哮喘(简称哮喘)中的发生发展已经引起高度关注,然而基于它们之间在哮喘发病机制中缺乏深度和系统性,本文就Th17/Treg细胞及其它们的主要相关因子IL-17、IL-10、中性粒细胞与哮喘关系的研究进展作一简要综述.     

The Th17/Treg balance is disturbed during aging

Aging is associated with multiple changes in the proliferative and functional abilities of the immune system which are not related to any pathology but consequences in immunosenescence and inflammaging.     

Restoring the Treg cell to Th17 cell ratio may alleviate HBV-related acute-on-chronic liver failure

AIM: To investigate the role of T helper 17 cells (Th17) and regulatory T cells (Treg) in hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF).METHODS: We enrolled 79 patients with HBV infection into the study, 50 patients with HBV-related ACLF and 29 patients with chronic hepatitis B (CHB), from the First Affiliated Hospital of Medical College from January 2009 to June 2012. The ACLF patients were diagnosed according to the criteria recommended by The 19th Conference of the Asian Pacific Association for the Study of the Liver in 2009. Twenty healthy individuals with a similar gender and age structures to the two patient groups were also included as the normal controls (NC). Of the 50 ACLF patients, 28 were subsequently classified as non-survivors: 19 patients died from multiorgan failure, 3 underwent liver transplantation, and 6 discontinued therapy during follow-up because of financial reasons. The remaining 22 ACLF patients whose liver and anticoagulation function recovered to nearly normal levels within the next 6 mo were classified as survivors. The number of circulating Treg and Th17 cells was determined upon diagnosis and during the 8th week of follow-up through flow cytometry. RESULTS: The percentage of circulating Treg cells in the ACLF group was significantly higher than that in the CHB group (5.50% ± 1.15% vs 3.30% ± 1.13%, P < 0.01). The percentages of circulating Th17 cells in the ACLF and the CHB groups were significantly higher than that in the NC group (6.32% ± 2.22% vs 1.56% ± 0.44%, P < 0.01; 3.53% ± 1.65% vs 1.56% ± 0.44%, P < 0.01). No significant difference in Treg cell to Th17 cell ratio was observed between the ACLF group and the CHB group (0.98 ± 0.44 vs 1.12 ± 0.64, P = 0.991), whereas those in the two HBV infection groups were significantly lower than that in the NC group (1.85 ± 1.22; both P < 0.01). The percentage of Treg cells in the survivors during the 8th week of follow-up was significantly lower than that during peak ACLF severity [total bili     

Imbalance of Th17 and Treg in peripheral blood mononuclear cells of active tuberculosis patients

Objective

Maintaining a right balance between Th17 and Treg might be critical to the immunopathogenesis of active tuberculosis (TB). This study aimed to assess whether the Th17/Treg balance is altered in active TB patients.

HBV相关慢加急性肝衰竭患者Th17、Treg变化及其与临床相关性

目的研究Th17、Treg及Th17/Treg在乙型肝炎相关慢加急性肝衰竭(ACHBLF)患者外周血的变化,及其与病情进展及预后的相关性。方法选取33例ACHBLF患者,30例慢性乙型肝炎患者及11名健康对照。用流式细胞技术检测血清中Th17、Treg频数,分析ACHBLF患者Th17、Treg频数的变化及其与TBil、ALT、PT等指标的相关性。结果ACBLF患者的Th17(1.96±0.99)%比CHB患者(0.59±0.40)%及健康对照者(0.26±0.20)%高(P0.05);ACHBLF的Th17/Treg(0.46±0.32)比CHB患者(0.12±0.11)及健康对照者(0.07±0.06)的高(P0.05);ACHBLF患者中,死亡者的Th17比存活者高;Th17细胞频数及Th17/Treg与PT、ALT及AST呈正相关(P0.05),与总胆红素无显著相关性,Th17/Treg与AFP呈正相关(P0.05)。结论 ACHBLF患者存在不同程度的免疫功能紊乱,Th17及Th17/Treg与病情进展相关,且对患者预后有重要价值,Th17越高预后越差。