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.     

Th17细胞及其相关细胞因子在IBD中研究新进展

炎症性肠病(inflammatory bowel disease, IBD)是一种慢性非特异性肠道炎症疾病,是一种免疫性疾病,目前尚无根治疗法,肠道免疫是炎症性肠病的研究重点,本文就Th17细胞及其相关细胞因子在炎症性肠病中的新研究进行综述,包括炎症性肠病病因、与适应性免疫的关系、与Th17细胞的关系, Th17细胞介绍、其相关细胞因子的介绍,和它们在IBD的研究状况,最后展望Th17细胞与IBD的未来研究方向.     

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.     

Th17细胞在炎症性肠病发生过程中的免疫病理作用

Th17细胞是最近发现的一种与Th1和Th2细胞亚群无关的新的辅助性T细胞亚群,其分化调节与多种细胞因子有关,可以清除特定的细胞外病原体起到保护作用,对自身抗原的特异性又可导致炎症和自身免疫性疾病发生.炎症性肠病的具体发病机制尚未阐清,但研究发现先天性和获得性免疫反应在肠道炎症中起着重要作用,而Th17细胞的发现有助于解释一些Th1/Th2轴中的异常现象,更好的认识Th17细胞在炎症性肠病发生过程中的免疫病理作用.     

IL-23在炎症性肠病中的免疫调节作用

IL-23属于IL-12家族, 他可由IL-12 P40亚单位和IL-23 P19亚单位通过二硫键形成的异二聚体分子, 通过结合T细胞表面上的受体复合物(IL-12Rb1和IL-23R构成)激活Stat1、Stat3及Stat4信号传导通路, 诱导IL-10和INF-γ的产生.IL-23还可以诱导初始CD4+ T细胞分化为具有致病性的Th17细胞, 并生成IL-17、IL-6和TNF-α, 引起慢性结肠炎症的发生. 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点.     

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在结缔组织病相关性间质性肺病中的意义

目的探讨外周血Th17及IL-17在结缔组织病相关性间质性肺疾病的表达及意义。方法收集23例正常对照组及28例病理类型为非特异性间质性肺炎(NSIP)的结缔组织病相关性间质性肺疾病(CTD-ILD)患者的外周血单个核细胞及血浆,分别检测PBMC中Th17的比例及血浆中IL-17的表达情况,并收集入组患者肺功能指标TLC(pre/ref%)及DLco(pre/ref%)数据。结果与正常对照组相比,CTD-ILD患者组Th17比例明显增加,差别具有统计学意义(P0.05),CTD-ILD患者IL-17细胞因子的浓度较正常对照组的血浆浓度明显增加(P0.01)。但CTD-ILD患者外周血Th17及IL-17与患者肺功能指标TLC(pre/ref%)及DLco(pre/ref%)之间均无显著相关性。结论在CTD-ILD患者体内Th17及其细胞因子IL-17明显升高,可能参与疾病的发生。     

白细胞介素-17A在风湿性疾病中的研究进展

风湿性疾病病因和发病机制复杂多样,主要表现为自身免疫反应异常引起的局部或全身炎症症状。目前IL-17A已在多种疾病领域有深入的研究,它的失衡与多种风湿性疾病的发病机制密切相关,包括SpA、RA、SLE、银屑病、炎症性肠病等。IL-17A和IL-17A产生细胞已成为治疗各种自身免疫病和炎症性疾病的重要靶点。本文拟收集近年...     

炎症性肠病患者外周血Th17细胞的变化及其临床意义

背景:Th17细胞是一类能特异性产生白细胞介素-17(IL-17)的CD4~+T细胞亚群,研究显示其参与了多种自身免疫性疾病的发病过程。目的:研究炎症性肠病(IBD)患者外周血Th17细胞比例和IL-17mRNA表达的变化,探讨Th17细胞在IBD发病机制中的意义。方法:纳入10例健康体检者(正常对照组)和53例IBD患者,其中克罗恩病(CD)25例,溃疡性结肠炎(UC)28例,以流式细胞术检测外周血Th17细胞比例,实时PCR检测外周血单个核细胞(PBMC)IL-17 mRNA表达水平。结果:IBD患者外周血Th17细胞比例明显高于正常对照组,其中活动期又明显高于缓解期,差异均有统计学意义(P0.05);其PBMC中IL-17 mRNA表达水平亦显著高于正常对照组(P0.05),但活动期与缓解期之间差异无统计学意义。结论:IBD患者外周血Th17细胞比例和IL-17 mRNA表达水平明显升高,Th17细胞参与了IBD的发生、发展过程,可能对临床疾病活动度的判断有一定意义。     

The Interleukin-23 / Interleukin-17 axis in intestinal inflammation

Although the precise aetiology of inflammatory bowel disease (IBD) remains unclear, recent discoveries have led to an improved understanding of disease pathogenesis. Whilst these findings have underscored the central role of innate and adaptive immune responses in intestinal inflammation, they have also precipitated a paradigm shift in the key cytokine pathways that drive disease. The prevailing dogma that IBD was mediated by interleukin (IL)-12-driven T-helper (Th)1 CD4 T cell responses towards the bacterial flora has been largely dispelled by findings that the closely related cytokine IL-23 appears to be the key mediator of intestinal inflammation. IL-23 is associated with a novel subset of IL-17-secreting CD4 T cells termed Th17 cells and rodent studies have implicated the IL-23/IL-17 axis in autoimmune inflammation. Genome-wide association studies in IBD patients have confirmed the predominant role of the IL-23 pathway, indicating that this could represent an important future therapeutic target.     

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.     

The IL-23/IL-17 pathway in inflammatory bowel disease

The etiology of inflammatory bowel disease is unknown but available evidence suggests that a deregulated immune response towards the commensal bacterial flora is responsible for intestinal inflammation in genetically predisposed individuals. IL-23 promotes expansion and maintenance of Th17 cells, which secrete the proinflammatory cytokine IL-17 and have been implicated in the pathogenesis of many chronic inflammatory disorders. Recent studies have shown that IL-23 also acts on cells of the innate immune system that can contribute to inflammatory cytokine production and tissue inflammation. A role for the IL-23/IL-17 pathway in the pathogenesis of chronic intestinal inflammation in inflammatory bowel disease has emerged from both animal and human studies. Here we aim to review the recent advances in this rapidly moving field.     

Contribution of the IL-17/IL-23 axis to the pathogenesis of inflammatory bowel disease

Inflammatory bowel diseases(IBDs) are chronic disorders of modern society, requiring management strategies aimed at prolonging an active life and establishing the exact etiology and pathogenesis.These idiopathic diseases have environmental, genetic,immunologic, inflammatory, and oxidative stress components. On the one hand, recent advances have shown that abnormal immune reactions against the microorganisms of the intestinal flora are responsible for the inflammation in genetically susceptible individuals. On the other hand, in addition to T helper cell-type(Th) 1 and Th2 immune responses,other subsets of T cells, namely regulatory T cells and Th17 maintained by IL-23 are likely to develop IBD. IL-23 acts on innate immune system members and also facilitates the expansion and maintenance of Th17 cells. The IL-17/IL-23 axis is relevant in IBD pathogenesis both in human and experimental studies. Novel biomarkers of IBD could be calprotectin,microRNAs, and serum proinflammatory cytokines.An efficient strategy for IBD therapy is represented by the combination of IL-17 A and IL-17 F in acute IL-17 A knockout TNBS-induced colitis, and also definite decrease of the inflammatory process in IL-17 F knockout, DSS-induced colitis have been observed.Studying the correlation between innate and adaptive immune systems, we hope to obtain a focused reviewin order to facilitate future approaches aimed at elucidating the immunological mechanisms that control gut inflammation.     

Th17 immune response in IBD: A new pathogenic mechanism

Although traditionally associated with exaggerated Th1 or Th2 cell response, the gut inflammation occurring in patients with IBD is also characterized by production of cytokines made by a distinct lineage of T helper cells, termed Th17 cells. The discovery that this new inflammatory T-cell subset drives immune-mediated pathology and that the antigen-presenting cell-derived IL-23 is necessary for amplifying Th17 cell-associated inflammation has contributed to elucidate new pathways of intestinal tissue damage as well as to open new avenues for development of therapeutic strategies in IBD.In this review, we discuss the available data regarding the involvement of Th17 cells and their interplay with other mucosal cell types in the modulation of intestinal tissue inflammation.     

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.     

Dysregulation of mucosal immune response in pathogenesis of inflammatory bowel disease

Inflammatory bowel disease(IBD)includes Crohn’s disease and ulcerative colitis.The exact etiology and pathology of IBD remain unknown.Available evidence suggests that an abnormal immune response against the microorganisms in the intestine is responsible for the disease in genetically susceptible individuals.Dysregulation of immune response in the intestine plays a critical role in the pathogenesis of IBD,involving a wide range of molecules including cytokines.On the other hand,besides T helper(Th)1 and Th2 cell immune responses,other subsets of T cells,namely Th17 and regulatory T cells,are likely associated with disease progression.Studying the interactions between various constituents of the innate and adaptive immune systems will certainly open new horizons of the knowledge about the immunologic mechanisms in IBD.     

Emerging role of IL-23/IL-17 axis in H pylori-associated pathology

Colonization of stomach by H pylori is followed by a marked infiltration of the mucosa with polymorphonuclear leukocytes, macrophages, and lymphocytes that very often remains asymptomatic, but in some circumstances can lead to the development of gastroduodenal ulceration, gastric carcinoma, and mucosa-associated lymphoid tissue lymphoma. The molecular mechanisms by which Hpylori triggers and maintains the local immune response are complex, but there is evidence that cytokines produced by both immune and non-immune cells contribute to amplify the ongoing inflammation. H pylori infection is associated with a marked mucosal induction of T helper （Th） type 1 and Th17-type cytokines that is governed by specific antigen-presenting cell-derived molecules, such as interleukin （IL）-12 and IL-23. In this paper, we will review the available data on the expression and role of IL-23 and IL-17 in H pylori-related gastritis.