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.     

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.     

T辅助细胞在炎症性肠病免疫发病机制中的研究进展

炎症性肠病(IBD)包括克罗恩病(CD)和溃疡性结肠炎(UC),免疫机制在其发病中的作用近年来受到密切关注,而T淋巴细胞中的T辅助细胞(Th),其亚型Th1、Th2、Th17、Treg和它们分泌的细胞因子在免疫调节炎症中发挥了至关重要的作用.此文就目前国内外关于Th细胞在IBD的免疫发病机制中的研究现状作一综述.     

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。     

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.     

CD4~+T细胞与炎症性肠病

CD4+T细胞按照分化及功能特征分为Th1、Th2、Th17和Treg4个主要的功能性亚群,各亚群间的免疫平衡紊乱与疾病的发生和发展相关。炎症性肠病是由遗传、环境、免疫等多因素参与的肠道慢性炎症性疾病,近年研究表明CD4+T细胞亚群之间的免疫失衡可能是其发病的最直接和最重要的因素,本文就该领域的新进展作一综述。     

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细胞与肺纤维化

Th17细胞是近年来新发现的一种能够分泌IL-l7的效应T细胞亚群,是一群重要的介导炎症反应的细胞。关于肺纤维化形成机理的研究,其具体的发病机制并不清楚,近年来Th17细胞与肺纤维化的关系研究有了非常重要的进展。有新的资料证明,Th17细胞与肺纤维化发病机理有密切关系。下面就Th17细胞产生的相关细胞因子及其在肺纤维化的作用等相关方面进行综述。     

白细胞介素家族在炎症性肠病发病中的意义

炎症性肠病（IBD）包括溃疡性结肠炎（UC）和Crohn病（CD）。根据所分泌细胞因子和介导免疫功能的不同，CD4^＋T细胞可分为1型辅助性T细胞（Th1细胞）和Th2细胞两型．Th1细胞以分泌干扰素（IFN）-1、白细胞介素（IL）-12等为主，Th2细胞以分泌IL-4、IL-10、IL-13等为主。Th1／Th2细胞亚群失衡一直被认为是IBD的发病机制之一。CD主要是，Th1型疾病，而UC主要是Th2型疾病。研究IL家族有助于探讨IBD的发病机制以及IL在IBD治疗中的作用。本文将IL家族分为致炎细胞因子和抗炎细胞因子两大类。分别介绍其在IBD发病中的意义。     

调节性T细胞及其分化因子IL-10治疗炎症性肠病的研究进展

CD+4 T细胞在炎症性肠病发病机制中起重要作用 ,Th1细胞因子介导的炎症病理改变类似于克罗恩病 ;Th2细胞因子介导的炎症病理改变类似于溃疡性结肠炎。在分化因子IL 10的作用下 ,调节性T细胞 (Tr1)又可分泌高水平的IL 10 ,通过旁观者抑制机制 ,抑制肠道粘膜免疫病理性损伤 ,达到治疗炎症性肠病的目的。     

Role of cytokines in inflammatory bowel disease

Inflammatory bowel disease （IBD）, which includes Crohn’s disease （CD） and ulcerative colitis （UC）, rep- resents a group of chronic disorders characterized by inflammation of the gastrointestinal tract, typically with a relapsing and remitting clinical course. Mucosal mac- rophages play an important role in the mucosal im- mune system, and an increase in the number of newly recruited monocytes and activated macrophages has been noted in the inflamed gut of patients with IBD. Activated macrophages are thought to be major con- tributors to the production of inflammatory cytokines in the gut, and imbalance of cytokines is contributing to the pathogenesis of IBD. The intestinal inflammation in IBD is controlled by a complex interplay of innate and adaptive immune mechanisms. Cytokines play a key role in IBD that determine T cell differentiation of Th1, Th2, T regulatory and newly described Th17 cells. Cytokines levels in time and space orchestrate the development, recurrence and exacerbation of the inflammatory process in IBD. Therefore, several cyto- kine therapies have been developed and tested for the treatment of IBD patients.     

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/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.     

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.     

Treg/Th17细胞分化失衡与炎症性肠病

炎症性肠病（IBD）的病因和发病机制尚未完全明确,初始CD4~＋T细胞分化异常在其发生、发展过程中起重要作用。初始CD4~＋T细胞可分化为调节性T细胞（Treg细胞）和Th17细胞,Treg/Th17细胞间的失衡将导致包括IBD在内的多种自身免疫病的发生。初始CD4~＋T细胞周围的细胞因子和芳香烃受体对维持该平衡起重要作用。本文就Treg细胞和Th17细胞及其与IBD的关系作一综述。     

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.     

Old and New Lymphocyte Players in Inflammatory Bowel Disease

Inflammatory bowel disease (IBD), encompassing Crohn’s disease and ulcerative colitis, is a chronic intestinal inflammatory disorder characterized by diffuse accumulation of lymphocytes in the gut mucosa as a consequence of over-expression of endothelial adhesion molecules. The infiltrating lymphocytes have been identified as subsets of T cells, including T helper (Th)1 cells, Th17 cells, and regulatory T cells. The function of these lymphocyte subpopulations in the development of IBD is well-known, since they produce a number of pro-inflammatory cytokines, such as interferon-γ and interleukin-17A, which in turn activate mucosal proteases, thus leading to the development of intestinal lesions, i.e., ulcers, fistulas, abscesses, and strictures. However, the immune mechanisms underlying IBD are not yet fully understood, and knowledge about the function of newly discovered lymphocytes, including Th9 cells, innate lymphoid cells, mucosal-associated invariant T cells, and natural killer T cells, might add new pieces to the complex puzzle of IBD pathogenesis. This review summarizes the recent advances in the understanding of the role of mucosal lymphocytes in chronic intestinal inflammation and deals with the therapeutic potential of lymphocyte-targeting drugs in IBD patients.