microRNA和Th17细胞在炎症性肠病形成与发展中的作用

炎症性肠病(IBD)是一种慢性非特异性肠道炎症性疾病,其病因及发病机制至今尚未完全阐明.近年研究表明Th17细胞是影响IBD发生发展的关键因素之一,同时microRNA(miRNA)与Th17细胞间存在着密切联系,且miRNA在IBD患者肠黏膜组织及外周血中存在特异性表达.此文就miRNA、Th17细胞与IBD的形成、发展的关系作一综述.     

Th17细胞在炎症性肠病发病机制作用的研究进展

炎症性肠病的病因和发病机制尚未完全明确。最近的研究表明,Th17细胞及与其相关的细胞因子、Th细胞亚群所导致的炎症过程在炎症性肠病的发生发展中起重要作用。本文就Th17的分化调控机制及Th17与其相关的细胞因子、Th细胞亚群在炎症性肠病的发病机制中的作用作一概述。     

Th17细胞及肠道内共生菌群在炎症性肠病中的作用

炎症性肠病(inflammatory bowe ldisease,IBD)是一种以慢性肠道炎症性疾病,病因未明,肠道黏膜异常的免疫反应在发病中有着重要作用.最近发现一类辅助T淋巴细胞Th17细胞,能在肠黏膜中大量分泌IL-17A和IL-17F.减少肠道Th17细胞数量和其相关的细胞因子的表达能够缓解肠道炎症反应,预示Th17细胞在IBD发病中起到一定作用.肠道共生菌与IBD的发病也有着密切关系,肠道共生菌群的变化可能导致Th17细胞的数量发生改变引起炎症,或者通过其他机制和途径诱发免疫紊乱,从而使得炎症得以发生.本文就Th17细胞的分化与其在IBD中的作用,以及共生菌群和Th17细胞之间的相互联系作一综述.     

Th细胞与炎症性肠病

Ｔ辅助细胞（Ｔｈ）是免疫应答中的主要反应细胞,在免疫调节中具有重要作用。ｈ细胞根据其分泌的细胞因子不同可分为Ｔｈ０、Ｔｈ１、Ｔｈ２、Ｔｈ３四个亚群。其中,Ｔｈ１／Ｔｈ２比例失衡在自身免疫疾病中的作用已得到证明。近年,Ｔｈ１／Ｔｈ２比例失衡在ＩＢＤ发病中的作用越来越爱到人们的重视,相信随着其研究的深入,有望为ＩＢＤ的治疗开辟崭新的途径。     

Th17细胞及IL-23在炎症性肠病中的研究进展

炎症性肠病(IBD)是一种病因和发病机制尚不清楚的发生在胃肠道的慢性非特异性炎症性疾病。大量证据表明先天性和获得性免疫系统的异常均对该疾病起着关键性作用。传统观点认为炎症性肠病与Th1细胞和Th2细胞所介导的免疫应答有关;但最新研究指出,体内Th17细胞以及白细胞介素IL-23的存在,与炎症性肠病的发生息息相关。本文对炎症性肠病中Th17细胞及IL-23的研究进展作一综述。     

Th细胞与炎症性肠病

T辅助细胞(Th)是免疫应答中的主要反应细胞,在免疫调节中具有重要作用。Th细胞根据其分泌的细胞因子不同可分为Th0、Th1、Th2、Th3四个亚群。其中,Th1/Th2比例失衡在自身免疫疾病中的作用已得到证明。近年,Th1/Th2比例失衡在IBD发病中的作用越来越受到人们的重视,相信随着其研究的深入,有望为IBD的治疗开辟崭新的途径。     

Th17/Treg失衡与炎症性肠病的关系

炎症性肠病(inflammatory bowel disease.IBD)的病因和发病机制尚未完全明确,肠道黏膜免疫系统异常反应所导致的炎症过程在发病中起重要作用.辅助性T细胞17(T helper 17 cells,Th17)可介导慢性炎症和自身免疫性疾病的发生,调节性T细胞(regulatory T cell,Treg)有抑制自身免疫的功能,二者存在相互转化的关系.有研究表明Th17/Treg转化平衡是维持肠道免疫稳态的重要因素,这可能是导致人类IBD的原因之一.最近研究表明TGF-β,IL-6和维甲酸(retinoic acid,RA)可能是调控二者平衡关系的重要因素.肠道菌群(intestinal flora)与IBD的发生发展关系密切,益生菌(probiotics)对IBD的治疗作用成为研究的热点.深化对Th17/Treg转化调控关系的研究是当前重要的研究课题.     

Th17细胞在肝脏疾病中的免疫病理作用

Th17细胞是效应性CD4+T细胞家族的新成员,由IL-6、TGF-β和IL-23等细胞因子诱导和维持分化,通过分泌IL-17、IL-21和IL-22等细胞因子参与炎症、自身免疫性疾病、肿瘤、移植排斥等过程。近年研究证实Th17细胞与多种肝脏疾病有关。     

IL-23／IL-17轴与炎症性肠病

传统观点认为,克罗恩病(CD)是与IL-12、IFN-γ、TNF细胞因子轴介导的Th1型反应相关的疾病,溃疡性结肠炎(UC)则与IL-4、IL-5、IL-13轴介导的Th2型反应关系密切.近期研究发现,IL-23/IL-17轴在炎症性肠病的发病机制中可能处于关键地位,并有望成为新的治疗靶标.IL-23诱导幼稚CD4 T细胞分化为高致病性的Th17细胞生成IL-17、IL-6和TNF-α,并引起结肠炎症.     

调节Th17/Treg细胞平衡的因素及其对炎症性肠病的影响

在炎症性肠病(inflammatory bowel disease, IBD)中,自身免疫由辅助性T细胞17(T helper cell 17, Th17)细胞驱动并被调节性T细胞(regulatory cells, Tregs)抑制,因此重塑Th17/Treg细胞的平衡对于治疗IBD至关重要.有许多因素参与影响了Th17/Treg平衡,其中包括TCR信号,共刺激信号,细胞因子信号,代谢水平,微生物群等.下面,本文将讲述它们在调节Th17/Treg平衡中的作用以及对IBD的影响.     

Potential role of Th17 cells in the pathogenesis of inflammatory bowel disease

The etiopathology of inflammatory bowel disease (IBD) remains elusive. Accumulating evidence suggests that the abnormality of innate and adaptive immunity responses plays an important role in intestinal inflammation. IBD including Crohn's disease (CD) and ulcerative colitis (UC) is a chronic inflammatory disease of the gastrointestinal tract, which is implicated in an inappropriate and overactive mucosal immune response to luminal flora. Traditionally, CD is regarded as a Th1mediated inflammatory disorder while UC is regarded as a Th2like disease. Recently, Th17 cells were identified as a new subset of T helper cells unrelated to Th1 or Th2 cells, and several cytokines [e.g. interleukin (IL)-21, IL-23] are involved in regulating their activation and differentiation. They not only play an important role in host defense against extracellular pathogens, but are also associated with the development of autoimmunity and inflammatory response such as IBD. The identification of Th17 cells helps us to explain some of the anomalies seen in the Th1/Th2 axis and has broadened our understanding of the immunopathological effects of Th17 cells in the development of IBD.     

炎症性肠病患者外周血辅助性T细胞1和辅助性T细胞17水平及其临床意义

 目的 探讨炎症性肠病（IBD）患者外周血Th1和Th17细胞水平对IBD发病及活动度的意义。方法 收集2011年5月至2012年7月健康对照者40例和IBD患者81例［其中克罗恩病（CD）39例,溃疡性结肠炎（UC）42例］,采集外周血标本。分离外周血单个核细胞,经PMA及伊屋诺霉素联合刺激、培养后,利用流式细胞仪检测Th1和Th17细胞在外周血CD⁺₄T细胞中的百分比,并结合临床资料分析其临床意义。结果 （1）CD组及UC组Th1细胞百分比［(38.32±16.18)%和(34.23±11.60)%］均明显高于健康对照组［(24.58±10.02)%］（P值均<0.01）,而CD组及UC组的差异无统计学意义;CD及UC缓解期患者的Th1细胞百分比均低于活动期患者［(26.50±9.24)%比(48.46±13.83)%,P<0.01;(30.05±7.41)%比(37.68±13.35)%,P<0.05］。（2）CD组及UC组Th17细胞百分比［(2.51±1.59)%和(4.15±2.75)%］均高于健康对照组［(1.44±0.73)%］（P值均<0.01）,且UC组这一比例高于CD组（P<0.01）;CD及UC活动期患者的Th17细胞百分比明显高于缓解期患者［(3.39±1.56)%比(1.48±0.81)%,(5.77±2.77)%比(2.18±0.59)%,P值均<0.01］。（3）UC组外周血Th17/Th1比值（0.14±0.11）高于CD组（0.08±0.06）和健康对照组（0.07±0.06）,P值均<0.01。结论 IBD患者外周血中Th1、Th17细胞占CD⁺₄T细胞比例较健康人群明显升高,且与IBD活动度密切相关。Th1和Th17细胞在IBD发病中可能具有重要作用。     

Functional relevance of T helper 17 (Th17) cells and the IL-17 cytokine family in inflammatory bowel disease

The recent discovery and characterization of T helper 17 cells (Th17) and their signature cytokines (IL-17) represents a hallmark in T-cell immunobiology by providing a new distinctive pathway for the communication between adaptive and innate immunity. From the six members of the IL-17 cytokine family presently known, at least two have evident proinflammatory qualities and are involved in several chronic inflammatory disorders, including inflammatory bowel disease (IBD). IL-17A and IL-17F are abundantly found in inflamed IBD mucosa, suggesting their pivotal role in IBD. However, the precise implication of IL-17 cytokine family members in IBD pathogenesis and the mechanisms regulating their secretion are incompletely understood. Importantly, recent findings suggest that beyond IL-17 production-Th17 cells may secret a plethora of other effector cytokines such as IL-21, IL-22, and IL-9- which is in part induced by its own IL-9 production. However, the use of anti-IL-17 therapeutic strategies in experimental models of chronic inflammation results in disease-ameliorating effects suggesting their potential use in IBD patients. In this review article we discuss the latest findings on the role of Th17 cells and IL-17 family members in IBD immunopathology, as well as research perspectives.     

Th17 cells in inflammatory conditions

CD4(+) T cells have been subdivided into different subsets, largely on the basis of the cytokines they produce. These subsets include Th1, Th2 and regulatory T cells. Recently, another population of T cells have been described, namely Th17, which are characterized by their production of IL-17. Two other important cytokines, which are related to each other, are associated with the development of Th cells, namely IL-12 and IL-23. While IL-12 plays a key role in the differentiation of na?ve T cells to Th1 cells, IL-23 promotes the expansion of Th17 cells. IL-12 and IL-23 are heterodimers with a shared subunit, p40. They furthermore bind to receptors which have unique and shared subunits. Several previous studies have evaluated the role of IL-12 in inflammatory diseases on the basis of p40. Therefore a reevaluation of the role of IL-12 and Th1 cells in a range of inflammatory conditions has been carried out. This new wave of studies has resulted in the recognition of the role of IL-23 and Th17 cells in inflammatory conditions, such as arthritis and inflammatory bowel disease. There is also the speculation about a possible role in type 1 diabetes.