IL-31及其受体在免疫相关性疾病中的作用

白细胞介素(interleukin, IL)-31是2004年新发现的一种细胞因子,其受体是由IL-31受体A(IL-31 receptor alpha, IL-31RA)和抑瘤素M受体(oncostatin-M receptor beta,OSMR)组成的异源性二聚体。最近的研究表明,IL-31通过刺激促炎性细胞因子...     

白细胞介素-37与自身免疫性疾病

白细胞介素(interleukin,IL)-37是新近发现的IL-1家族细胞因子,对固有免疫和适应性免疫均有抑制作用.IL-37主要表达于中性粒细胞、淋巴细胞、巨噬细胞、单核细胞、组织上皮细胞、角质形成细胞和树突状细胞.最近大量研究显示,IL-37在许多自身免疫性疾病患者或动物模型中表达异常并发挥关键作用,如系统性红斑狼疮、炎症性肠病、强直性脊柱炎、支气管哮喘、银屑病、Graves病以及类风湿性关节炎等.深入研究IL-37的生物学功能、信号转导途径及作用机制将为IL-37在自身免疫性疾病的治疗提供新思路和靶点.     

调节性B细胞与自身免疫性疾病

由于B细胞具有分泌抗体的能力,因此常被认为是免疫应答的正向促进因素,然而,研究发现,某些B细胞也能通过分泌调节性细胞因子(如IL-10、TGF-β等)来负向调节免疫过程,以及通过细胞间接触的方式直接作用于致病性T细胞.这种B细胞被定义为调节性B细胞(regulatory B cells,Bregs).许多学者已经阐释了Breg细胞在炎症和自身免疫疾病的动物模型中的调节作用.     

IL-17与自身免疫性疾病相关研究进展

白细胞介素17（interleukin-17，IL-17）及IL-17家族是近年来发现的一组促炎症性细胞因子，具有强大的招募中性粒细胞的作用，调节并促进多种炎性介质的产生，参与了机体多种炎性疾病，与感染、肿瘤、过敏、移植及自身免疫性疾病均有密切关系。本文就IL-17的发现及近年IL-17与自身免疫性疾病的相关研究进展加以综述。     

自身基因与自身免疫性疾病

自身免疫性疾病与自身免疫不同，后者是由于年龄等因素造成的正常情况，一般来讲是可逆的或是生理性的。而前者是由于基因、病毒、激素和神经内分泌免疫调节因素的改变造成的对机体正常功能的损伤。自身基因的概念把自身免疫性疾病的成因，归结到了免疫反应调节基因的水平，从最根本上，提出了了解和控制自身免疫性疾病的新途径。本文拟从目前已经明确的自身基因（如Ｆａｓ和ｂｃｌ－２）入手，通过分析这些基因与细胞凋亡的关系，说     

转化生长因子β与自身免疫性疾病

TGF－β是一大类多效能细胞因子，分布及作用范围十分广泛，并参与了许多重要的生理及病理过程，其负性免疫调节作用是近年研究的热点。本文重点介绍了TGF－β在自身免疫性疾病的发病及治疗中的最新研究进展。     

超抗原与自身免疫性疾病

超抗原是指一些细菌外毒素和逆转录病毒的基因产物，包括Ｔ细胞超抗原（Ｔ－ＳＡｇ）和Ｂ细胞超抗原（Ｂ－ＳＡｇ）。它与自身免疫性疾病密切相关，参与免疫性疾病的致病过程。这为自身免疫性疾病发病机制的研究提供了新途径。     

转录因子FOXP3与自身免疫性疾病

Foxp3是Forkhead/winged helix家族的新成员,定位于X染色体上,通过forkhead结构域与DNA特定位点结合,调节目的基因的活化与表达。其编码产物为scurfin蛋白,可能是CD4 CD25 调节性T细胞(简称CD4 CD25 Treg)特异性标志,对CD4 CD25 Treg的增殖分化及功能发挥起重要作用。CD4 CD25 Treg同时表达CD4和CD25,介导机体特异性免疫耐受,抑制机体自身免疫性疾病、肿瘤、病毒感染及器官移植免疫等。Foxp3基因突变或缺失可引起风湿、类风湿、系统性红斑狼疮、X-相关综合征等疾病;Foxp3基因过表达可诱导机体对肿瘤、病毒及器官移植等产生免疫耐受。Foxp3表达上调,可维持免疫耐受、抑制排斥反应和自身免疫性疾病;Foxp3表达下调,降低机体免疫耐受,可治疗肿瘤、器官移植及慢性病毒感染。     

Updated assessment of the prevalence, spectrum and case definition of autoimmune disease

Autoimmune diseases are heterogeneous with regard to prevalence, manifestations, and pathogenesis. The classification of autoimmune diseases has varied over time. Here, we have compiled a comprehensive up-to-date list of the autoimmune diseases, and have reviewed published literature to estimate their prevalence. We identified 81 autoimmune diseases. The overall estimated prevalence is 4.5%, with 2.7% for males and 6.4% for females. For specific diseases, prevalence ranges from 1% to <1/10(6). Considering all diseases in the class, the most common mean age-of-onset was 40-50 years. This list of autoimmune diseases has also yielded information about autoantigens. Forty-five autoimmune diseases have been associated with well-defined autoantigens. Of the diseases with known autoantigens, 33.3% had highly repetitive sequences, 35.6% had coiled-coil arrangements and 57.8% were associated with cellular membranes, which means that based on these structural motifs alone, autoantigens do not appear to be a random sample of the human proteome. Finally, we identified 19 autoimmune diseases that phenocopy diseases arising from germline mutations in the corresponding autoantigen. Collectively, our findings lead to a tentative proposal for criteria for assigning autoimmune pathogenesis to a particular disease.     

Vaccination against IL-17 suppresses autoimmune arthritis and encephalomyelitis

Interleukin 17 is a T cell-derived cytokine that induces the release of pro-inflammatory mediators in a wide range of cell types. Recently, a subset of IL-17-producing T helper cells (Th17) distinct from Th1 and Th2 cells has been described, which constitutes a new T cell polarization state. Aberrant Th17 responses and overexpression of IL-17 have been implicated in a number of autoimmune disorders including rheumatoid arthritis and multiple sclerosis. Molecules blocking IL-17 such as IL-17-specific monoclonal antibodies have proved to be effective in ameliorating disease in animal models. Hitherto, active immunization targeting IL-17 is an untried approach. Herein we explore the potential of neutralizing IL-17 by active immunization using virus-like particles conjugated with recombinant IL-17 (IL-17-VLP). Immunization with IL-17-VLP induced high levels of anti-IL-17 antibodies thereby overcoming natural tolerance, even in the absence of added adjuvant. Mice immunized with IL-17-VLP had lower incidence of disease, slower progression to disease and reduced scores of disease severity in both collagen-induced arthritis and experimental autoimmune encephalomyelitis. Active immunization against IL-17 therefore represents a novel therapeutic approach for the treatment of chronic inflammatory diseases.     

Association studies of the IL-23R gene in autoimmune thyroid disease in the Japanese population

Autoimmune thyroid diseases (AITDs), including Graves' disease (GD) and Hashimoto's thyroiditis (HT), are caused by interplays of genetic factors and environmental triggers. Interleukin-23 and its receptor (IL-23R) guide T cells towards the Th17 phenotype. IL-23R single nucleotide polymorphisms (SNPs) have been shown to be associated with several autoimmune diseases, including Crohn's disease and rheumatoid arthritis, and Graves' ophthalmopathy (GO) in Caucasians. To determine whether variants in the IL-23R gene are associated with AITDs in Japanese, 464 Japanese AITD patients (290 with GD, 174 with HT) and 179 matched Japanese control subjects were genotyped for four SNPs spanning the IL-23R gene. SNPs rs11209026 and rs7530511 were genotyped using TaqMan allelic discrimination assays and SNPs rs2201841 and rs10889677 were genotyped using a fluorescent-based restriction fragment length polymorphism method. Case-control association studies were performed using the χ² and Fisher's exact tests with Yates correction. Of the four SNPs rs11209026 was non-polymorphic in our dataset. The other three SNPs were not associated with GD or GO or HT in our Japanese population. These results suggest that the IL-23R gene is associated with AITDs only in a specific ethnic group.     

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.     

巨噬细胞活化与自身免疫病

巨噬细胞“活化”在免疫反应、机体自稳、疾病的发生发展与预后中发挥重要作用,与多种自身免疫病的发生发展密切相关.但目前对其活化的定义、分类、鉴定等尚未有统一的标准,因此研究巨噬细胞活化的定义、分类、表面标记的改变、更清楚地了解巨噬细胞活化在自身免疫病中发挥的重要作用很有必要.     

IL-22在自身免疫病中作用的研究进展

IL-22为IL-10家族成员之一.作为一种新型细胞因子,其与自身免疫性疾病关系密切.最近大量证据表明IL-22参与了多种自身免疫性疾病,如系统性红斑狼疮、类风湿性关节炎、多发性硬化、干燥综合征、银屑病等.然而在不同的自身免疫性疾病中IL-22所发挥的作用不尽相同,可能起致病性作用,也可能起保护性作用.因此以IL-22作为靶点为多种自身免疫性疾病的治疗提供了新的思路.     

IL-23在眼部疾病中的研究进展

白细胞介素(interleukin,IL)-23作为IL-12家族中的重要成员具有强大的促炎作用,是一种重要的炎症因子。目前IL-23已经被发现与多种自身免疫性疾病和许多炎性疾病具有密切关系。越来越多的研究表明,IL-23在很多眼部疾病的发生发展过程中也起到关键作用。文章对IL-23在角膜病、眼表疾病、葡萄膜炎、糖尿病...