血吸虫及其相关蛋白与自身免疫性疾病

自身免疫性疾病(ADs)是以特定的靶器官或多个器官系统的慢性损害和功能障碍为特征,临床上缺乏有效的治疗方法,目前发病率逐年升高,严重威胁人类健康。现有数据显示,血吸虫感染或注射血吸虫相关蛋白可能保护或减轻机体免受自身免疫性疾病的损害。研究学者已经建立相应的小鼠自身免疫疾病模型,证实了注射血吸虫蛋白具有诱导宿主Th2免疫偏移,下调Th17反应,并诱导旁路途经活化的巨噬细胞,从而减轻自身免疫性疾病,具有肯定的治疗效果。在这篇综述中,我们总结了血吸虫感染及血吸虫相关蛋白与减轻Th1介导的自身免疫性疾病之间的关系,力争明确其潜在的免疫保护机制。     

血吸虫及其相关产物在宿主免疫调节中的作用

血吸虫可通过合成、分泌或者排泄多种具有免疫调节功能的分子影响宿主的免疫系统,主要表现为促进Th2免疫效应,抑制Th1/Th17免疫效应.血吸虫感染过程中,其免疫调节效应可以调控宿主固有免疫和适应性免疫,使其能够逃避宿主的免疫攻击,而在人体内长期存活.研究显示血吸虫感染对于过敏性疾病、自身免疫性疾病以及同种异体免疫反应等...     

Th17细胞与自身免疫性疾病研究进展

Th17细胞能产生白细胞介素(IL)-17、IL-6和肿瘤坏死因子(TNF)-α等细胞因子,介导炎症反应,参与自身免疫病和移植排斥等的发生发展[1].本文仅就Th17细胞的生物特性、功能及在自身免疫性疾病中的作用综述如下.     

Th17细胞与肝脏疾病

辅助性T细胞（Th细胞）根据产生细胞因子和生物学功能分为Th1和Th2细胞。最近研究发现了一种与Th1和Th2细胞亚群不同的活化CD4^＋T细胞亚群-Th17细胞。TGF-8与IL-6或IL-21的协同作用,诱导Th17细胞分化。IL-12家族的IL-23在促进IL-17分泌、增强Th17细胞效应功能方面发挥重要作用,而RORγt是其特异性转录因子。分化成熟的Th17细胞可以分泌IL-17A、IL-17F、IL-21、IL-22、IL-6、TNF—α等多种细胞因子,在介导炎性反应（防御病原菌感染）、自身免疫性疾病、肿瘤、移植排斥反应等过程中发挥重要作用。Th17细胞也为研究肝脏疾病的发病机制及防治策略提供了新思路和方向。     

寄生虫感染与“卫生假说”关系研究进展

近年来,许多发达国家感染性疾病发病率不断下降,但自身免疫性疾病和过敏性哮喘发病率呈逐年上升趋势。"卫生假说"的提出为基于寄生虫感染治疗自身免疫性疾病和过敏性哮喘提供了新思路。大量流行病学和动物实验数据均显示,寄生虫感染能有效抑制糖尿病、多发性硬化症、炎症性肠病、类风湿性关节炎、过敏性哮喘等疾病发生。寄生虫感染和"卫生假说"间存在复杂的潜在机制,其中调节性T(Treg)细胞和Th17细胞的各自作用和相互调节逐渐成为研究热点。本文阐述了寄生虫感染与"卫生假说"关系研究进展,并简要概述Treg细胞和Th17细胞在其中的作用。     

Th17细胞与肝脏疾病

辅助性T细胞(Th细胞)根据产生细胞因子和生物学功能分为Th1和Th2细胞.最近研究发现了一种与Th1和Th2细胞亚群不同的活化CD4+T细胞亚群-Th17细胞.TGF-β与IL-6或IL-21的协同作用,诱导Th17细胞分化.IL-12家族的IL-23在促进IL-17分泌、增强Th17细胞效应功能方面发挥重要作用,而RORγt是其特异性转录因子.分化成熟的Th17细胞可以分泌IL-17A、IL-17F、IL-21、IL-22、IL-6、TNF-α等多种细胞因子,在介导炎性反应(防御病原菌感染)、自身免疫性疾病、肿瘤、移植排斥反应等过程中发挥重要作用.Th17细胞也为研究肝脏疾病的发病机制及防治策略提供了新思路和方向.     

蠕虫及虫源性分子对自身免疫性疾病的保护作用

机体接触包括蠕虫在内的病源微生物机会减少,尤其在幼年时期免疫系统失去病源微生物的塑造和协调,是导致西方发达国家自身免疫性疾病和过敏性疾病发病率迅速增高的主要原因之一。蠕虫感染能激发强烈的Th2 免疫应答,可以改善Th1 介导的自身免疫性疾病的临床症状和病理过程。日益增多的流行病学及实验研究证实了蠕虫对自身免疫性疾病及过敏性疾病的保护作用,显示了优异的临床应用价值。蠕虫感染能激发强烈的Th2 免疫应答,可以改善Th1 介导的自身免疫性疾病的临床症状和病理过程。目前,蠕虫感染诱导的宿主Th2 免疫偏移已成为感染免疫调节研究的重要模型,并显示了优异的临床应用价值,具有诱人的临床应用前景。然而其负向免疫调控的机制至今尚未明了。本文回顾近年来蠕虫及其分子调节自身免疫性疾病的国内外研究进展,着重探讨蠕虫感染及其分子发挥免疫抑制作用的可能机制。     

Th17在自身免疫性肝炎病理形成中的作用

自身免疫性肝炎（AIH）是T细胞介导的一种慢性肝脏炎症性疾病,以肝脏特异性组织学改变、高免疫球蛋白、循环自身抗体及对免疫抑制剂治疗有反应为其主要特征,基因易感性、病毒分子模拟、自身免疫反应等均被认为与AIH发病机制相关,目前AIH的治疗以抑制肝脏免疫反应为主,但AIH的发病机制至今仍尚未完全明确。Th17细胞为近年来新近发现的Th辅助细胞,它所分泌的细胞因子在多种自身免疫性疾病中均有不同程度的升高,虽然在肝脏疾病中的作用仍处于研究阶段,但Th17的发现无疑对免疫介导的肝脏疾病乃至AIH发病机制的进一步研究有所帮助,也为疾病的治疗提供了新的线索。     

CD4+ T细胞亚群在血吸虫感染中的动态变化及功能研究进展

血吸虫病是一种主要以肝、肠虫卵肉芽肿和随之伴随的纤维化为主要特征的免疫病理性疾病。一般认为,CD4+ T细胞亚群在抗血吸虫感染及免疫调控过程中起着重要作用。其中辅助性T（T helper,Th）细胞1（Th1）、2（Th2）是主要的效应性CD4+ T细胞亚群,而调节性T（Regulatory T,Treg）细胞在血吸虫感染免疫病理机制中总体起免疫下调作用,新近发现的Th17细胞也积极参与抗血吸虫免疫反应。随着血吸虫感染的进展,这4种CD4+ T细胞亚群数量及功能呈现不同变化趋势,但均对血吸虫感染发生、发展及纤维化病理进程起重要的调控作用。此外,这些CD4+ T细胞亚群之间也存在复杂的相互调节（Cross?talk）。本文就血吸虫感染过程中Th1、Th2、Th17 和 Treg细胞亚群及其效应细胞因子的动态变化与功能的研究进展作一综述。     

CDCD4~+T细胞亚群在血吸虫感染中的动态变化及功能研究进展

血吸虫病是一种主要以肝、肠虫卵肉芽肿和随之伴随的纤维化为主要特征的免疫病理性疾病。一般认为,CD4+T细胞亚群在抗血吸虫感染及免疫调控过程中起着重要作用。其中辅助性T(T helper,Th)细胞1(Th1)、2(Th2)是主要的效应性CD4+T细胞亚群,而调节性T(Regulatory T,Treg)细胞在血吸虫感染免疫病理机制中总体起免疫下调作用,新近发现的Th17细胞也积极参与抗血吸虫免疫反应。随着血吸虫感染的进展,这4种CD4+T细胞亚群数量及功能呈现不同变化趋势,但均对血吸虫感染发生、发展及纤维化病理进程起重要的调控作用。此外,这些CD4+T细胞亚群之间也存在复杂的相互调节(Cross-talk)。本文就血吸虫感染过程中Th1、Th2、Th17和Treg细胞亚群及其效应细胞因子的动态变化与功能的研究进展作一综述。     

Treg/Th17平衡与血吸虫感染免疫

血吸虫感染可诱导调节性T细胞（Treg）和Th17型免疫反应。研究表明,Treg和Th17细胞及其平衡在血吸虫感染中具有非常重要的作用。Treg细胞抑制宿主体内过度病理反应,并有助于血吸虫逃避宿主的免疫攻击;而Th17细胞促进血吸虫感染过程中的免疫病理发展。本文就Treg/Th17平衡与血吸虫感染免疫关系的研究进展作一综述。     

Role of CD4(+) CD25(+) regulatory T cells in T helper 2 cell-mediated allergic inflammation in the airways

It has recently been shown that CD4(+) CD25(+) T cells are immunoregulatory T cells that prevent CD4(+) T cell-mediated organ-specific autoimmune diseases. To determine whether CD4(+) CD25(+) T cells downregulate Th2 cell-mediated allergic inflammation in the airways, we studied antigen-induced eosinophil recruitment in the airways in BALB/c Rag-2(-)(/-) mice transferred with CD4(+) CD25(+) T cell-depleted or unfractionated T cells from ovalbumin-specific TCR transgenic mice. Antigen-induced eosinophil recruitment into the airways was significantly decreased in the mice transferred with CD4(+) CD25(+) T cell-depleted splenocytes as compared with those transferred with unfractionated splenocytes. On the other hand, the depletion of CD4(+) CD25(+) T cells increased antigen-induced neutrophil and T cell recruitment in the airways of the mice. The depletion of CD4(+) CD25(+) T cells also decreased antigen-induced IL-4 and IL-5 production in the airways of the mice. Finally, the depletion of CD4(+) CD25(+) T cells prevented antigen-induced Th2 cell differentiation in vitro but increased the differentiation of Th1 cells. These results indicate that CD4(+) CD25(+) T cells modulate the Th1 and Th2 cell balance toward Th2 cells and thus upregulate Th2 cell-mediated allergic inflammation in the airways.     

Th17 and allergy.

The identification of novel helper T (Th) cell subsets, i.e., IL-17-producing Th cells (Th17 cells) and regulatory T cells (Treg cells), provided new insight into our understanding of the molecular mechanisms involved in the development of infectious and autoimmune diseases as well as immune responses, and thus led to revision of the classic Th1/Th2 paradigm. Several current lines of evidence from gene-deficient mice indicate that IL-17 and Th17 cells, but not IFN-gamma and Th1 cells, are responsible for the development of autoimmune diseases such as murine arthritis and encephalomyelitis, which have classically been considered to be Th1-mediated disorders. Th17 cells may also contribute to the pathogenesis of classically recognized Th2-mediated allergic disorders. In this review, we summarize the current knowledge regarding IL-17 and Th17 cells and discuss their potential roles in the pathogenesis of allergic disorders.     

Prevalence of atopy in children with type 1 diabetes mellitus, hepatitis B virus carriers, and healthy children: role of T helper 1 (Th1)-type immune response.

The prevalence of allergic diseases such as asthma, hay fever, and atopic dermatitis has increased over the past few decades, especially in developed countries. They are characterized by a chronic inflammatory reaction mediated by T helper 2 (Th2) cells. Two common chronic diseases of childhood-an autoimmune disease, type 1 diabetes mellitus (DM), and a chronic viral infection, hepatitis B virus (HBV) carriers-are associated with a Th1-dominant and Th1-insufficient cytokine profile, respectively. The purpose of this study was to analyze the frequency of allergic disease in patients with type 1 DM and, in HBV carriers, to evaluate the role of Th1-type immune response in atopy and allergic disease. The study included patients with type 1 DM (group I, n = 52), HBV carriers (group III, n = 47), and a healthy control group (group III, n = 209). Participants were screened for allergic disease and atopic sensitization. Symptoms of asthma, eczema, and atopy were found more commonly in HBV carrier children compared with those with DM and healthy controls. This study supports the Th1/Th2 model. The prevalence of allergic disease and atopy is decreased in Th1-mediated autoimmune disease, type 1 DM, and, conversely, is increased in insufficient Th1 response, chronic HBV carriers. Additional studies are needed to evaluate the effect of atopy and allergic diseases in glycemic control and long-term complications in patients with type 1 DM and the effect of atopy on progression of chronic HBV infection.     

T辅助细胞17与气道变态反应性疾病

T辅助细胞17（helper T17,Th17）是近年来新发现的独立的辅助T细胞亚群,以分泌白细胞介素17（intedeukin17,IL-17）为主要特征。现已证实Th17在自身免疫性疾病及感染等中发挥着重要的作用。随着对Th17细胞分化及调节的深入研究,人们发现其在以Th2主导的变态反应性疾病中也扮演着重要的角色。     

Alteration of IL-17 related protein expressions in experimental autoimmune myocarditis and inhibition of IL-17 by IL-10-Ig fusion gene transfer.

BACKGROUND: T-helper (Th)1/Th2 cytokine balance plays an important role in the pathogenesis of myocarditis. Recently, some studies indicate that interleukin (IL)-17, known as a T cell (Th17)-derived proinflammatory cytokine, is the major mediator of tissue inflammation in inflammatory and autoimmune diseases. Experimental autoimmune myocarditis (EAM) is a T cell-mediated autoimmune disease; however, the pathogenic role of IL-17 in the development of rat EAM remains largely unknown. METHODS AND RESULTS: In the present study, alterations of IL-17-related protein expressions were investigated and then the effect of hydrodynamic-based delivery of plasmid DNA encoding the IL-10-Ig gene on rat EAM and the effect of IL-10-Ig on IL-17 was evaluated. The results showed that IL-17 was expressed more highly than IFN-gamma expressed by Th1 cells in alphabetaT cells and the peaks of IL-17 related protein expression in the heart were the early phase of EAM. Moreover, we observed that IL-10-Ig gene therapy was effective in controlling EAM and that IL-10-Ig significantly suppressed the expression of IL-17 as well as other proinflammatory cytokines, IL-1beta and TNF-alpha, in IL-1-stimulated splenocytes cultured from EAM rats. CONCLUSIONS: IL-17 is highly produced by alphabetaT cells in the early phase of EAM hearts and IL-17 inhibition might be a possible mechanism of the amelioration of EAM by IL-10-Ig treatment. These data suggest that IL-17 produced by Th17 plays an important role in the pathogenesis of rat EAM.