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.     

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细胞和肠道菌群在炎症性肠病发病中的作用

炎症性肠病(IBD)是一种自身免疫性疾病,发病机制尚未明确,目前认为是由宿主基因、肠道微生物以及生活环境等因素综合作用,引发机体异常免疫应答所致。近年来,Th17细胞与IBD的关系成为研究热点,且越来越多的研究表明,肠道菌群对Th17细胞及其相关细胞因子的调节与IBD发病密切相关。本文就Th17细胞和肠道菌群在IBD发病中的作用作一综述。     

调节性T细胞在炎症性肠病中的研究进展

炎症性肠病(IBD)是一种非特异性肠道炎症性疾病,其发病与自身免疫功能紊乱有关.Th1/Th2失衡是导致IBD的重要因素之一.然而,Th1/Th2理论并不能充分阐明IBD的发病机制.近几年来,越来越多的研究显示,调节性T细胞在炎症性肠病的发生发展中起重要的作用.本文就近年来调节性T细胞在炎症性肠病中作用的研究进展作一综述.     

Treg细胞和Th17细胞在炎症性肠病治疗中的作用

炎症性肠病(IBD)是一类非特异性肠道炎症性疾病,肠道黏膜免疫失衡是诱导IBD发生的主要原因之一。调节性T细胞(Treg细胞)是重要的免疫调控细胞,辅助性T细胞17(Th17细胞)参与宿主免疫防御,两者之间的平衡是维持肠道免疫稳态的重要因素。本文就Treg细胞和Th17细胞在IBD治疗中的作用作一综述。     

Th17与肠黏膜免疫关系的研究进展

辅助性T细胞17(T helper cell 17,Th17)是近年来新发现的一种辅助T细胞亚群,其分化与多种细胞因子及转录因子有关,他能分泌白介素(interleukin,IL)-17、IL-22等多种细胞因子,在肠黏膜屏障中既有促进炎症进展又有组织保护作用.益生菌已被证实在肠道中有抗炎作用,其作用的发挥可能与抑制T h17细胞活动有关,但T h17细胞数量的稳定则需要肠道共生菌的存在.本文对Th17细胞的分化及其在肠黏膜免疫中的作用作一概述.     

白细胞介素17A与炎症性肠病的关系研究进展

炎症性肠病(inflammatory bowel disease,IBD)包括溃疡性结肠炎(ulcerative colitis,UC)和克罗恩病(Crohn’s disease,CD),是一种反复发作的慢性炎症性肠道疾病,其发病机制目前尚不十分清楚。通常认为免疫系统功能异常与IBD的发生、发展关系密切,Th17是一种T淋巴细胞亚群,成熟的Th17可以分泌IL-17A、IL-17F、IF-21、IL-22等一系列炎症因子,其中IL-17A在肠上皮黏膜损伤过程中起重要作用。随着对IL-17A研究的进一步深入,针对IL-17A分泌过程进行调节干预也成为IBD治疗的新思路。     

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。     

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.     

炎症性肠病病理生理学机制研究进展

炎症性肠病(inflammatory bowel disease,IBD)的表观遗传学研究发现DNA甲基化是发生在基因组Cp G二核苷酸的胞嘧啶上的变化,溃疡性结肠炎(ulcerative colitis,UC)有16%的遗传可能性;IBD的免疫学研究发现本病存在由CD4+Th1、Th2、Th17、Treg淋巴细胞介导的免疫反应;肠道菌群失调是IBD的继发性改变,但其在黏膜免疫反应及炎症的持续及放大效应中发挥重要作用;肠黏膜在抵御肠道菌群的过程中发挥重要作用,回肠克罗恩病(Crohn’s disease,CD)与防御素表达减少或功能缺陷有关,且肠黏膜紧密连接(tight junction,TJ)的复杂性受损。     

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.     

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.     

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.     

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。     

Can control of gut microbiota be a future therapeutic option for inflammatory bowel disease?

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract encompassing two main clinical entities, Crohn’s disease and ulcerative colitis. Accumulated evidence indicates that an aberrant immune activation caused by the interplay of genetic susceptibility and environmental impact on the gut microbiota may be involved in the pathogenesis of IBD. Rapid advances in next-generation sequencing technology have enabled a number of studies to identify the alteration of the gut microbiota, termed dysbiosis, in IBD. Moreover, the alteration in the metabolites derived from the gut microbiota in IBD has also been described in many studies. Therefore, microbiota-based interventions such as fecal microbiota transplantation (FMT) have attracted attention as a novel therapeutic option in IBD. However, in clinical trials, the efficacy of FMT for IBD remains controversial. Additional basic and clinical studies are required to validate whether FMT can assume a complementary role in the treatment of IBD. The present review provides a synopsis on dysbiosis in IBD and on the association between the gut microbiota and the pathogenesis of IBD. In addition, we summarize the use of probiotics in IBD and the results of current clinical trials of FMT for IBD.     

Role of the novel Th17 cytokine IL-17F in inflammatory bowel disease (IBD): upregulated colonic IL-17F expression in active Crohn's disease and analysis of the IL17F p.His161Arg polymorphism in IBD

BACKGROUND: Interleukin (IL)-17F, produced in IL-23R-expressing Th17 cells, is a novel member of the IL-17 cytokine family. Given the association of IL23R with inflammatory bowel disease (IBD), we characterized the role of IL-17F in IBD including its intestinal gene expression and the effect of the IL17F p.His161Arg polymorphism on disease susceptibility and phenotype of Crohn's disease (CD) and ulcerative colitis (UC). In addition, we analyzed the IL17F p.His161Arg polymorphism for potential epistasis with IL23R and NOD2/CARD15 variants. METHODS: Intestinal IL-17F mRNA expression was measured by quantitative polymerase chain reaction (PCR). Genomic DNA from 1682 individuals (CD: n = 499; UC: n = 216; controls: n = 967) was analyzed for the presence of the IL17F p.His161Arg polymorphism, the 3 NOD2 variants, p.Arg702Trp, p.Gly908Arg, and p.Leu1007fsX1008, and 10 CD-associated IL23R variants. RESULTS: Intestinal IL-17F mRNA expression was 4.4-fold increased in inflamed colonic lesions compared to uninflamed biopsies in CD (P = 0.016) but not in UC. However, the mean intestinal IL-17F mRNA expression was higher in UC than in CD (P < 0.0001). The IL17F p.His161Arg substitution was observed with similar frequencies in IBD patients and controls and was not associated with a certain disease phenotype, but weakly associated with a low body mass index (BMI; P = 0.009) and an earlier age of disease onset (P = 0.039) in UC. There was no evidence for epistasis between the IL17F p.His161Arg polymorphism and IBD-associated single nucleotide polymorphisms within the IL23R gene. CONCLUSIONS: Intestinal IL17F gene expression is increased in active CD. The IL17F p.His161Arg polymorphism is not associated with IBD susceptibility and has no epistatic interaction with CD-associated IL23R variants.     

Pivotal roles of the interleukin-23/T helper 17 cell axis in hepatitis B

T helper 17 (Th17) cells are a newly identified subset of T helper cells that play important roles in host defense against extracellular bacteria, as well as in the pathogenesis of autoimmune disease. Research interest in these cells was piqued when hepatitis B virus (HBV)-infected patients were found to have significantly elevated Th17 cell frequency, and it was proposed that these proinflammatory effectors may promote the HBV disease process. Subsequent studies have revealed that Th17 cells drive immune-mediated pathology of HBV infection, and that IL-23 amplifies the Th17 cell responses and liver inflammation. As a result, new pathways of HBV-mediated liver damage have been elucidated, along with promising new targets of molecular therapeutic strategies. Ongoing research is also providing significant insights into the target cells and underlying mechanisms of Th17-secreted cytokines, including IL-17A, IL-21 and IL-22. Future studies are expected to fully uncover the cytokine-related mechanisms mediating HBV-induced liver inflammation, and to determine the yet unknown cell source of IL-23. This review will draw upon the most up-to-date available data to discuss the putative roles and detailed mechanisms of IL-23/Th17 cell axis in HBV infection-mediated liver pathogenesis.