Th17细胞与肝脏疾病的研究进展

机体免疫系统是抵抗外来病原体和各种损害的防御系统,根据CD4^＋T细胞的功能经典地分为辅助性T细胞（Th1、Th2）、细胞毒性T细胞以及调节性T细胞（Treg）3个亚群。Th1介导细胞免疫,Th2介导体液免疫,而Treg则在维护机体免疫平衡中发挥重要作用。然而随着对自身免疫性疾病的研究,发现一群不同于Th1、Th2、Treg的新型CD4^＋T细胞亚群——Th17细胞。已证实Th17细胞与清除胞外病原体、炎症、自身免疫性疾病和肿瘤的发生发展有密切联系。随着人们对肝炎、肝纤维化和肝癌等肝病认识不断加深,这种新型的Th17细胞在这些疾病中发生发展的作用机制也不断的被研究者所关注。     

大肠癌肿瘤微环境中Th17细胞与调节性T细胞的作用及临床意义

大肠癌是全球最常见的恶性肿瘤之一,大肠癌的发生、发展与肠内慢性炎症(CRC)密切相关,而部分炎症细胞及其分泌的细胞因子在这一过程中扮演着重要角色,肿瘤浸润效应T细胞与多种类型肿瘤病人的预后密切相关,辅助性T细胞17(Th17)是新近发现的一类CD4+效应T细胞亚群,在炎症、自身免疫性疾病和肿瘤中发挥积极作用.调节性T细胞(Tregs)在功能上是T细胞的免疫抑制亚群,在自身免疫耐受和抗肿瘤免疫中起重要作用.Th17细胞和Treg细胞之间的动态平衡在保持免疫调控功能中至关重要.     

Th17细胞与自身免疫性疾病

Th17细胞是近年发现的不同于Th1细胞和Th2细胞的新型CD4^＋T细胞亚群。活化的Th17细胞可分泌IL—17、肿瘤坏死因子-α（TNF—α）、IL-6、粒-单核细胞集落刺激因子（GM—CSF）等多种促炎症因子,Th17细胞不适当的激活与多种自身免疫性疾病和过敏性疾病密切相关。在体内阻断Th17细胞的分化、扩增及其相关细胞因子可预防、延缓或阻止自身免疫性疾病的发生、发展。     

Th17细胞在肿瘤中的作用

Th17细胞是新发现的一群不同于Th1与Th2细胞的CD4+T细胞亚群.Th17细胞以IL-23依赖的方式分泌白细胞介素(IL)-17,在慢性炎症与自身免疫性疾病中发挥重要作用.自2005年发现以来,Th17细胞受到了广泛关注,并已成为免疫学研究的热点.近年来的研究显示,Th17细胞也参与了肿瘤免疫,但对于其是促进肿瘤发生发展还是抑制肿瘤发展尚无定论.     

IL-21在Th17细胞炎症反应中的作用

Th17细胞是新近发现的T淋巴细胞亚群.作为不同于Th1、Th2的细胞亚群,已经被证实在自身免疫病、感染、炎症等疾病中发挥重要作用.IL-21作为Th17细胞的自分泌调节因子,在Th17细胞功能的维持、抑制Th1、调节性T细胞(Treg)分化等方面发挥关键作用.Th17细胞能够自分泌产生IL-21,从而促进自身分化过程...     

Th9细胞与自身免疫性疾病

Th1、Th2、Th17和调节性T细胞（Treg）亚群是CD4＋T细胞亚群中的重要成员,其参与了人类及动物自身免疫性疾病的发病过程.既往认为,IL-9是由CD4＋Th2细胞分泌的细胞因子,是机体免疫应答中重要的调节因子.最近研究表明,机体内可能存在着一群新型的具有分泌IL-9和IL-10能力的CD4＋Th细胞亚群,称之为＂Th9＂细胞.该细胞亚群与自身免疫性疾病的相关性尚不清楚.     

Th17细胞与自身免疫性疾病关系的研究进展

CIM+辅助性T细胞(Th)通常可分为Th0、Th1、Th2和Th3等细胞亚群.Th1细胞过去一直被认为是介导迟发型超敏反应、引起组织损伤的主要细胞.近年来发现一群主要分泌白细胞介素-17(IL-17)、不同于Th1/Th2的新型CD4+T细胞亚群-11117细胞.Th17细胞与自身免疫性疾病、肿瘤、炎性反应和移植排斥等的发生发展关系密切.     

Th22细胞在自身免疫性疾病中作用的研究进展

Th22细胞为新近发现的一群不同于Th1、Th2及Th17细胞的CI4+T细胞亚群,其表型为CCR6+CCR4+CCR10+,主要分泌IL-22,但不生成IL-17和IFN-γ.Th22细胞有其独特的基因表达谱及功能谱,协同其它淋巴细胞亚群构成机体错综复杂的免疫调控网络,以维持机体稳态.新近文献报道,Th22细胞及其效应分子IL-22在自身免疫性疾病发生与发展中扮演重要角色,深入探讨Th22细胞生物学特性及其介导的自身免疫性疾病有助于阐明相关疾病病理生理机制,亦为其治疗提供坚实的理论基础.     

Th17细胞与支气管哮喘关系的研究进展

Th17细胞是新近研究发现的一类CD4＋T细胞亚群,多方面研究表明其与许多自身免疫性疾病和促炎症反应的发生与发展密切相关,也有大量研究表明Th17与Th2、Th1及Treg细胞共同参与哮喘发病。Th17／IL-17不仅介导哮喘中性粒细胞性气道炎症,也调节嗜酸粒细胞和巨噬细胞性等炎症,与特应性体质的发生、气道高反应性和气道黏液的分泌均密切相关。本文就Th17细胞在支气管哮喘疾病中的作用进行综述。     

Th9细胞与自身免疫性疾病关系的研究进展

Th9细胞是不同于已知的Th1细胞、Th2细胞及Th17细胞等一种新型的CD4+辅助性T细胞亚群,因其主要分泌白介素9(IL-9)而得名。目前很多研究已证实Th9细胞及其分泌的IL-9在多种自身免疫性疾病及过敏性疾病的发生发展中发挥重要作用。通过对Th9细胞及其分泌的IL-9的研究,将会为自身免疫性疾病的防治提供重要的理论依据。本文就Th9细胞与自身免疫性疾病的研究进展进行综述。     

The role of Th17 cells and regulatory T cells in Coxsackievirus B3-induced myocarditis

IL-17-producing (Th17) and regulatory T (Treg) cells have been well established in the pathogenesis of many inflammatory diseases. To assess whether Th17 and Treg were altered in acute virus-induced myocarditis (AVMC) mice, we assessed Th17/Treg functions on different levels in AVMC. It was shown that the expression of splenic Th17 cells and Th17-related cytokines (IL-17A, IL-21) markedly increased. Interestingly, the expression of splenic Treg cells and Treg-related cytokines (TGF-β, IL-10) also significantly increased. Using neutralization of IL-17 in the AVMC, we found that Treg cells roughly decreased compared with isotype control mice. However, T cells and perforin dramatically increased, followed by a marked reduction in CVB3 replication. The results suggested that Th17 cells possibly contributed to viral replication through the action of Treg cells in mediating T cells and perforin response in AVMC.     

Th17与自身免疫性疾病

当初始CD4+T细胞接受抗原刺激时,在不同的细胞因子环境中分化为不同的淋巴细胞亚群.Th17作为一种新的T细胞亚群是在TGF-β与IL-6存在时经由孤独核受体(ROB)-γt途径分化而来,而当环境中仅有TGF-β时却分化为CD4+CD25+Foxp3+调节性T细胞(Tr).与Th1一样,Th17被认为在自身免疫性疾病和炎症反应的发生和进展中都发挥重要的病理作用,相反,Tr则起着抗炎和免疫负性调节的作用.因此Th1及Th17倾向的免疫应答可能导致炎症反应与自身免疫性疾病的发生和进展,故在体内阻断其相关的细胞因子IL-17、IL-6等则可使Th1、Th17及Tr重新保持平衡而对自身免疫性疾病产生治疗作用.     

细菌溶解产物口服治疗通过影响T细胞平衡改善PM2.5所致大鼠气道炎症

目的本研究旨在从Th1/Th2及Th17/Treg平衡轴的角度探讨PM2.5暴露及细菌溶解产物Broncho-Vaxom(BV)治疗与健康大鼠气道炎症的关系。方法PM2.5暴露组鼻内滴注PM2.5混悬液,口服生理盐水;BV治疗组暴露与PM2.5暴露组相同,口服BV溶液;对照组均用生理盐水代替。对大鼠鼻黏膜进行组织病理学检查;用流式细胞仪和酶联免疫吸附试验(ELISA)检测Th1/Th2/Th17/Treg细胞的表达和功能。结果PM2.5暴露组大鼠鼻黏膜出现炎症细胞浸润;Th2细胞和Th17细胞显著上调,Treg细胞显著下调;血清中相关细胞因子IL-4、IL-5、IL-13及IL-17显著升高,IFN-γ和IL-10显著下降。BV干预后鼻黏膜炎性细胞浸润减少、Th细胞相关免疫失衡减轻。结论PM2.5可诱导健康大鼠产生气道炎症,PM2.5暴露所诱导的气道炎症可能与Th1/Th2和Th17/Treg细胞免疫失衡有关,BV可减轻PM2.5诱导的气道炎症及Th细胞相关免疫失衡。     

类风湿性关节炎患者外周血Th17/Treg细胞比率失衡的研究

目的:观察类风湿性关节炎(RA)患者外周血Th17细胞与Foxp3+CD4+CD25+调节性T(Treg)细胞的平衡状态与疾病状态的关系,初步阐明Th17/Treg细胞比率失衡在RA发病机制中的作用和意义。方法:流式细胞术(FCM)检测RA患者和健康人外周血中Th17细胞和Foxp3+CD4+CD25+Treg细胞的比率。结果:活动期RA患者外周血CD3+CD4+T细胞和Th17细胞的比率均明显高于健康对照组(P均0.05);而Foxp3+CD4+CD25+Treg细胞的比率明显低于健康对照组(P0.05)。随疾病活动性的增加,Th17细胞表达增高(P0.05);而Foxp3+CD4+CD25+Treg细胞表达降低,但无统计学意义(P0.05)。结论:RA患者外周血T细胞紊乱以CD4+T细胞的增加为主,Th17细胞比率的增加和Foxp3+CD4+CD25+Treg细胞比率的降低所致的Th17/Treg细胞比率失衡,可能在RA的发生发展中起重要作用。     

Th17/Treg及其相关细胞因子在结肠癌中的表达并与肿瘤分期的相关性

研究结肠癌患者肿瘤组织中Th17细胞、Treg细胞及患者外周血中相关细胞因子的表达水平,探讨其表达与肿瘤分期的相关性及可能机制。运用流式细胞分析(FACS)技术检测30例结肠癌肿瘤组织及癌旁正常组织中Th17细胞及Treg细胞的比例;采用逆转录聚合酶链反应技术(RT-PCR)检测20例结肠癌患者外周血中Th17、Treg相关细胞因子IL-23和IL-10的表达水平。结果显示结肠癌肿瘤组织中Th17细胞和Treg细胞的比例明显高于癌旁正常组织(P<0.05),进展期肿瘤组织中Treg细胞的比例高于早期(P<0.05),而Th17细胞的比例较早期无明显差异(P>0.05),进展期肿瘤组织中Th17/Treg细胞的比例比早期偏低(P<0.05)。结肠癌患者外周血中IL-23、IL-10的mRNA水平升高,与健康对照组差异明显(P<0.05),且进展期与早期结肠癌IL-10mRNA的表达水平差异显著(P<0.05),而IL-23mRNA在两组间无明显差异(P>0.05)。随着结肠癌病程的进展,肿瘤组织内Th17细胞及Treg细胞的比例逐渐升高,且Treg细胞比Th17细胞升高更加明显。相关细胞因子IL-23和IL-10在患者外周血中的变化趋势和Th17、Treg细胞在肿瘤组织中的变化趋势相一致,提示Th17、Treg细胞在结肠癌的表达可能与肿瘤免疫微环境中相关的细胞因子调节有关。     

The Expression of Th17-Associated Cytokines in Human Acute Graft-versus-Host Disease

The role of Th17 cells and Th17-associated cytokines in the development of acute graft-versus-host disease (aGVHD) in clinical allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients is not well established. In the current study, a cohort of 69 allo-HSCT patients was examined for the percentages of Th17 and FoxP3⁺ Treg cells and the expressions of RORγt and FoxP3 in peripheral blood mononuclear cells (PBMCs). The Th17 percentage and RORγt expression were significantly higher, whereas Treg percentage and FoxP3 expression were significantly lower in severe aGVHD (grade 3 to 4) and mild aGVHD (grade 1 to 2) patients than in patients without aGVHD (grade 0) and healthy donors. We then investigated the expressions of Th17-associated cytokines, including TGF-β, IL-6, IL-1β, IL-17, IL-21, IL-22, IL-23, as well as IL-23R in the PBMCs of patients after allo-HSCT. The expressions of IL-17 and IL-22 in CD4⁺ T cells were also examined. The results showed that the expressions of IL-6, IL-1β, IL-17, IL-21, IL-23, and IL-23R were all increased, whereas IL-22 expression was decreased in aGVHD patients. The changes were also correlated with the severity of aGVHD. We also investigated the dynamic changes of Th17/Treg cells and Th17-associated cytokines in patients during the onset and resolution of aGVHD. The results demonstrated a reciprocal relationship between Treg and Th17 cells. Th17-associated cytokine expressions, namely IL-17 and IL-23, were closely related to the occurrence and resolution of aGVHD. We conclude that the dynamic balance between the Th17 and FoxP3⁺ Treg cells and the changes of Th17-associated cytokines could be the indicators of the disease progression and promising candidates of prognostic biomarkers of aGVHD.     

Modulatory effect of intravenous immunoglobulin on Th17/Treg cell balance in women with unexplained recurrent spontaneous abortion

Recurrent spontaneous abortion (RSA) is a growing problem worldwide. In a majority of cases, the cause remains unknown but there is increasing evidence that immunologic factors play an important role. Intravenous immunoglobulin (IVIg) therapy has been proposed to have immune modulatory effects and therefore been applicable for the treatment of patients with RSA. Although its efficacy is still controversial, several recent studies suggest that IVIg treatment may improve pregnancy outcomes. CD4⁺ T cells and their related cytokines play an important role in maternal‐fetal immune regulation, and an imbalance of Th17/Treg cell ratio has been proposed as a cause for RSA. We review the scientific evidence supporting a modulatory effect of IVIg on Th17/Treg cell balance and discuss the potential mechanisms how IVIg might enhance Treg cells function. We propose that correction of Th17/Treg cell dysregulation could be one of the mechanisms that can explain the positive therapeutic effects of IVIg therapy. Consequently, selecting patients with abnormal Th17/Treg cell ratios could increase the success of IVIg therapy.     

补肾益气方对不明原因反复自然流产患者外周血Foxp3~+ Treg/Th1/Th17细胞的影响

为探讨补肾益气方对反复自然流产患者外周血Treg/Th1/Th17的影响,选取我院自然流产专科门诊30例反复自然流产(recurrent spontaneous abortion,RSA)患者,诊断为正常妊娠后开始服用补肾益气方中药,采用流式细胞仪检测服药前后Treg/Th1/Th17细胞数量,ELISA方法检测外周血TNF-α、IFN-γ、IL-4、IL-10及IL-17水平变化。结果显示中药治疗后RSA患者外周Treg细胞数量上升(5.85±2.76),明显高于服药前(3.26±1.19),P<0.05。Th1和Th17细胞数量下降(8.38±4.38和0.95±0.15),明显低于治疗前(23.59±8.14和1.58±0.71),P<0.05。IL-10和IL-4水平显著上升(P<0.05),TNF-α、IFN-γ和IL-17水平明显下降(P<0.05)。实验表明,补肾益气方中药能够调控Treg/Th1/Th17细胞水平,改变母体细胞因子分泌格局,保护胎儿不被排斥。     

Leptin deficiency impairs maturation of dendritic cells and enhances induction of regulatory T and Th17 cells

Leptin is an adipose‐secreted hormone that plays an important role in both metabolism and immunity. Leptin has been shown to induce Th1‐cell polarization and inhibit Th2‐cell responses. Additionally, leptin induces Th17‐cell responses, inhibits regulatory T (Treg) cells and modulates autoimmune diseases. Here, we investigated whether leptin mediates its activity on T cells by influencing dendritic cells (DCs) to promote Th17 and Treg‐cell immune responses in mice. We observed that leptin deficiency (i) reduced the expression of DC maturation markers, (ii) decreased DC production of IL‐12, TNF‐α, and IL‐6, (iii) increased DC production of TGF‐β, and (iv) limited the capacity of DCs to induce syngeneic CD4⁺ T‐cell proliferation. As a consequence of this unique phenotype, DCs generated under leptin‐free conditions induced Treg or T_H17 cells more efficiently than DCs generated in the presence of leptin. These data indicate important roles for leptin in DC homeostasis and the initiation and maintenance of inflammatory and regulatory immune responses by DCs.