Th9细胞及相关因子的研究进展

CD4+辅助性T(Th)细胞参与宿主防御反应,维持免疫细胞动态平衡。初始CD4+T细胞分化为不同细胞亚群由不同细胞因子决定。与亚群相关的相对特异的典型细胞因子不仅能够诱导初始CD4+T细胞分化,亦可作为感受器启动该细胞亚群发挥细胞免疫作用,还可以直接参与免疫应答反应。Th9细胞是一种CD4+辅助T细胞亚群,分泌白细胞介素9,已经发现多种细胞因子与Th9细胞有关,Th9细胞对自身免疫性疾病的作用越来越受到重视。本文就Th9细胞的生物学特性、分化相关信号分子及对自身免疫性疾病的作用综述如下。     

Th9细胞与肝纤维化的研究进展

Th9细胞是近年新发现的Th细胞亚群。这种细胞亚群的诱导分化受到多种细胞因子与转录因子的影响,且与其他亚群间存在相互影响。IL-4和转化生长因子β是诱导Th9分化的关键细胞因子,PU.1和干扰素调节因子4为其特异的转录因子。Th9细胞主要通过分泌大量IL-9细胞因子在自身免疫性疾病、过敏性疾病以及抗寄生虫感染等过程中发挥重要作用。近年来的研究发现Th9细胞可能促进肝纤维化的发生,本文就Th9细胞与肝纤维化关系的研究现状做一综述。     

Th17细胞在自身免疫性疾病中的研究进展

辅助性T细胞17(Th17)是近年来发现的一类新的CD4~+辅助T细胞亚群,其增殖和分化不同于Th1和Th2细胞。Th17表达特异性的核转录因子维甲酸孤儿受体-γt(RORγt),并能分泌特异性细胞因子IL-17。Th17作为一种促炎性细胞,广泛参与多种自身免疫性疾病、感染性疾病、肿瘤以及慢性炎症性疾病的发生、发展;同时Th17分泌的炎症性细胞因子IL-17在各类疾病中具有至关重要的作用。本文就Th17细胞的生物学特征、分化以及其在自身免疫性疾病中的研究进展做一综述。     

Th9细胞的生物学及其与疾病的关系

Th9细胞是新近发现的一种新的CD4+T细胞亚群,其分化和增殖明显不同于已知的各型CD4+T细胞,且其特异地分泌IL-9,以尚不明了的方式参与不同免疫过程。我们拟从转录因子,细胞因子,免疫效应等方面对Th9细胞的研究进展做一简单综述。     

Th17细胞的分化调控与自身免疫性疾病

Th17细胞是最近发现的一种在分化和功能上均不同于Th1和Th2的新型CD4＋T细胞亚群.该群细胞以主要分泌细胞因子IL-17而得名.IL-6、TGF-β、IL-21及IL-23等对Th17细胞的分化调控发挥重要作用.研究表明,Th17细胞可参与多种自身免疫性疾病的发生、发展与转归.     

Th17细胞与Graves’病

Th17细胞是近几年研究发现的一类不同于Th1和Th2细胞亚群的新型CD4^＋效应T细胞。该类细胞是由天然T细胞前体分化而来,具有独立分化和发育调节机制,在其分化过程中需要IL-6和转化生长因子。B、转录因子RORα及STAT3等的参与,主要分泌IL-17A、IL-17F、IL-22等多种细胞因子,并参与多种炎症、自身免疫性疾病的发生和发展。Graves’病（GD）是一种器官特异性自身免疫病,Th2细胞介导的体液免疫在其发病中起着重要作用。近来有研究提示IL-23／Th17轴亦参与GD的发展。因此了解Th17细胞分化的影响因素、产生的细胞因子以及在免疫性疾病GD中的作用具有重要的临床意义。     

Th17细胞及其相关因子与自身免疫平衡的作用进展

Th17细胞是新近发现的不同于Th1细胞和Th2细胞的新型CD4+T细胞亚群。Th17细胞的分化受转录因子RORγt、IL-23、TGF-β和IL-6等细胞因子的调控。Th17细胞的特性与其分泌的IL-17的生物学效应密切相关。Th17细胞参与了多种自身免疫性疾病的发生发展。     

Th9与哮喘

人类和动物疾病模型中CD4+Th细胞在获得性免疫应答中发挥着重要的作用。在很长的一段时间内,我们对于其亚群的认识局限于Th1和Th2细胞。但是随着我们对于其分化特点、机制的认识快速进步,最近几年其新的亚群包括Treg(调节性T细胞)和Th17细胞陆续被发现。新近研究表明,在某些特定条件(如IL-4和TGF-β同时存在)下,存在着不同于Th1、Th2和Th17的CD4+Th细胞亚群,即Th9细胞。他们有着独特的分化机制和免疫应答机制,可以产生大量的IL-9。IL-9参与Th2类炎症及病理反应,故其曾被广泛地看作Th2类细胞因子,但与其他Th2类细胞因子如IL-4、IL-5、IL-13等相比,IL-9拥有不同类型的调节作用和生物活性。IL-9是参与免疫应答和免疫调节的重要细胞因子,其可以作用于多种免疫细胞和炎症细胞,在过敏反应中发挥重要作用。本文结合动物和人类过敏疾病模型,简要综述Th9细胞的生物学特征以及其在过敏性哮喘中可能的作用机制。     

Th9细胞与自身免疫性疾病

Th1、Th2、Th17和调节性T细胞（Treg）亚群是CD4＋T细胞亚群中的重要成员,其参与了人类及动物自身免疫性疾病的发病过程.既往认为,IL-9是由CD4＋Th2细胞分泌的细胞因子,是机体免疫应答中重要的调节因子.最近研究表明,机体内可能存在着一群新型的具有分泌IL-9和IL-10能力的CD4＋Th细胞亚群,称之为＂Th9＂细胞.该细胞亚群与自身免疫性疾病的相关性尚不清楚.     

Th17与自身免疫性疾病

当初始CD4+T细胞接受抗原刺激时,在不同的细胞因子环境中分化为不同的淋巴细胞亚群.Th17作为一种新的T细胞亚群是在TGF-β与IL-6存在时经由孤独核受体(ROB)-γt途径分化而来,而当环境中仅有TGF-β时却分化为CD4+CD25+Foxp3+调节性T细胞(Tr).与Th1一样,Th17被认为在自身免疫性疾病和炎症反应的发生和进展中都发挥重要的病理作用,相反,Tr则起着抗炎和免疫负性调节的作用.因此Th1及Th17倾向的免疫应答可能导致炎症反应与自身免疫性疾病的发生和进展,故在体内阻断其相关的细胞因子IL-17、IL-6等则可使Th1、Th17及Tr重新保持平衡而对自身免疫性疾病产生治疗作用.     

T helper-9 cells and Interleukin-9 in transplantation: The open question

The role of main TCD4+ lymphocyte subsets including T helper 1 (Th1), Th2, Th17, and T regulatory cells in transplantation has already been described; however, the implication of newly defined lineages such as Th22, Th9, and T follicular helper cells in alloimmune responses remain to be elucidated. In addition to the low number of studies, most evidence about the role of these cells in transplantation has been obtained from experimental studies, which might be insufficient or irrelevant for clinical interpretations. In the present article, we have reviewed the studies that have investigated the role of Th9 and its principal cytokine interleukin-9 (IL-9) in allograft rejection and tolerance induction. However, the findings tend to be controversial since some investigations demonstrate positive effects of Th9 on transplantation outcomes whereas others are suggestive of its detrimental influences. A similar challenge is presented by IL-9 as both advantages and disadvantages of IL-9 expression in allografts have been reported. Moreover, different organs appear to be affected in different ways by Th9 cells and IL-9. Therefore, more research particularly in human patients is required to provide sufficient data for drawing a concrete conclusion about the implication of Th9 and IL-9 in transplantation.     

The Role of T cell Immunoglobulin and Mucin Domain‐3 in Immune Thrombocytopenia

T cell immunoglobulin and mucin domain‐3 (TIM‐3), originally identified as a T helper (Th) 1‐specific type I membrane protein, plays a vital role in Th1 immunity and tolerance induction through interaction with its ligand, galectin‐9. The binding of TIM‐3 by galectin‐9 serves to downregulate Th1 responses. Moreover, the regulatory function of TIM‐3 has been extended to other cells, such as Th17 cells, CD4⁺CD25⁺ regulatory T cells (Tregs), CD8⁺ T cells and certain innate immune cells. Previous studies have acknowledged that the TIM‐3 pathway is involved in the pathogenesis of several human autoimmune diseases, such as systemic lupus erythematous, rheumatoid arthritis and aplastic anaemia. Moreover, genetic data suggest a role for TIM‐3 in human autoimmune diseases. However, in immune thrombocytopenia (ITP), a common Th1‐ and possibly Th17‐biased autoimmune disorder, the role of TIM‐3 has not been explored. Recently, our data have demonstrated that TIM‐3 expression is reduced in ITP patients, and we have found a potential link between ITP and the TIM‐3 pathway. In this article, we discuss and speculate on the role of the TIM‐3 pathway in ITP.     

Th9细胞和白细胞介素-9在自身免疫性疾病中的研究进展

Th9细胞亚群是近几年发现的一种新型效应性CD4+T淋巴细胞亚群,其主要以分泌细胞因子白细胞介素(IL)-9为特征.其分泌的IL-9可作用于不同的炎性细胞和组织细胞,产生不同的生物学效应.研究显示,Th9细胞和IL-9参与许多自身免疫性疾病如自身免疫性肠炎、自身免疫性脑脊髓炎(EAE)、系统性红斑狼疮(SLE)、银屑病等的发病机理,在疾病的发生和发展中起着重要的作用.     

Role of Th17 cells and IL-17 in lung transplant rejection

In the past decade, advances in immunology have led to the recognition that T cell differentiation is not simply Th1 or Th2 but involves differentiation to other subsets, such as T regulatory cells, T follicular helper cells, and Th17 cells. Th17 cells, characterized by production of IL-17, IL-22, and IL-21, have been implicated in the pathogenesis of autoimmune diseases, like rheumatoid arthritis and multiple sclerosis, but also play an important role in host defense and mucosal immunity. IL-17, with its pleiotropic effects on stromal cells, as well as hematopoietic cells, has long been recognized as a possible mediator of rejection after lung transplantation. Recent data have implicated IL-17 and Th17 cells in the development of autoimmunity and chronic rejection after lung transplantation in both animal models and humans. In this review, we will discuss the current data on Th17 and the prospects for the future for lung transplantation.     

Th17 and regulatory T cell balance in autoimmune and inflammatory diseases

This review focuses on the biology of T helper 17 (Th17) and regulatory T (Treg) cells and their role in inflammatory diseases, such as rheumatoid arthritis. Th17 cells represent a pro-inflammatory subset whereas Treg cells have an antagonist effect. Their developmental pathways are reciprocally interconnected and there is an important plasticity between Th17 and Treg cells. These features implicate that the Th17/Treg balance plays a major role in the development and the disease outcomes of animal model and human autoimmune/inflammatory diseases. During these diseases, this balance is disturbed and this promotes the maintenance of inflammation. Targeting the Th17/Treg imbalance can be performed at different levels such as inhibition of pro-inflammatory cytokines and their receptors, of pathogenic cells or their specific signaling pathways. Conversely, direct effects include administration or induction of protective cells, or stimulation of their specific pathways. Several clinical trials are underway and some positive results have been obtained.     

Interleukin‐9 and T helper type 9 cells in rheumatic diseases

Interleukin (IL)‐9 is a 28‐30 kDa monomeric glycosylated polypeptide belonging to the IL‐7/IL‐9 family of proteins that bind to a composite receptor consisting of the private receptor IL‐9R and the IL‐2 receptor, gamma (IL‐2RG), a common gamma subunit shared by the receptors of many different cytokines. The IL‐9R is expressed widely and IL‐9 impacts a number of effector cells, such as effector T cells, B cells, innate lymphoid cells, mast cells, polymorphonuclear cells, epithelial cells and smooth muscle cells, playing an important role in regulating inflammatory immunity. The critical role of IL‐9 in promoting cellular and humoral immune responses makes it an important focus of potential therapeutic interventions. Recently, a defined subset of T helper type cells, Th9 cells, has been identified by the potent production of IL‐9. The involvement of the Th9 cell subset has been described in many types of inflammatory diseases, namely atopic diseases, helminth infections, experimental autoimmune encephalomyelitis and ulcerative colitis. In this review, we summarize the IL‐9 biological activities, highlighting roles for IL‐9 and Th9 cells in rheumatoid and psoriatic arthritis, systemic vasculitis, systemic lupus erythematosus and systemic sclerosis.     

Translational Mini‐Review Series on Th17 Cells: Function and regulation of human T helper 17 cells in health and disease

T helper (Th) cell have a central role in modulating immune responses. While Th1 and Th2 cells have long been known to regulate cellular and humoral immunity, Th17 cells have been identified only recently as a Th lineage that regulates inflammation via production of distinct cytokines such as interleukin (IL)-17. There is growing evidence that Th17 cells are pathological in many human diseases, leading to intense interest in defining their origins, functions and developing strategies to block their pathological effects. The cytokines that regulate Th17 differentiation have been the focus of much debate, due primarily to inconsistent findings from studies in humans. Evidence from human disease suggests that their in vivo development is driven by specialized antigen-presenting cells. Knowledge of how Th17 cells interact with other immune cells is limited, but recent data suggest that Th17 cells may not be subject to strict cellular regulation by T regulatory cells. Notably, Th17 cells and T regulatory cells appear to share common developmental pathways and both cell types retain significant plasticity. Herein, we will discuss the molecular and cellular regulation of Th17 cells with an emphasis on studies in humans.     

Role of Th1 and Th17 cells in organ-specific autoimmunity

CD4(+) IFN-gamma-producing Th1 cells have long been associated with the pathogenesis of many organ-specific autoimmune diseases; however, the observation of disease in mice deficient in molecules involved in Th1 cell differentiation raised the possibility that other effector T cells were responsible for inducing autoimmunity. Recently, a new CD4(+) effector T cell subset that produces IL-17 (Th17) has emerged. The fact that Th17 cells are highly auto-pathogenic has fueled a debate as to what role, if any, Th1 cells play in the induction of tissue inflammation and autoimmune disease. This review will discuss the respective roles of the Th1 and Th17 subsets in organ-specific autoimmunity.