Th17细胞与自身免疫病的研究进展

Th17是新近发现的CD4+T细胞亚群,分泌IL-17介导组织炎症,与Th1、Th2同属于前炎性Th细胞.TGF-β、IL-6、IL-1β、IL-23刺激天然CD4+T细胞表达ROR-γt分化为Th17.IL-23诱导Th17分泌IL-17,IL-27抑制Th17分化,Th1细胞与Th17细胞分化增生有着密切关系.目前已发现Th17在人类自身免疫病中发挥重要作用,阻断病理性免疫反应中的关键性的细胞因子,逆转Th17/Th1极化,能够改善自身免疫病.     

急性胰腺炎患者Th17/Treg细胞平衡与IL-23/IL-17炎症轴的关系

目的 研究急性胰腺炎患者辅助性T细胞17(Th17)/调节性T细胞(Treg)细胞平衡与白细胞介素23(IL-23)/白细胞介素17(IL-17)炎症轴的关系。方法 选择2018年6月—2021年6月河北省中医院收治的63例急性胰腺炎患者为观察组,另于同期选择63名健康成年人作为对照组,其中观察组依据急性胰腺炎严重程度分为轻度急性胰腺炎(MAP)19例、中度急性胰腺炎(MSAP)23例、重度急性胰腺炎(SAP)11例。检测两组外周血Th17、Treg细胞比例和血清IL-23、IL-17水平,比较观察组和对照组、不同严重程度急性胰腺炎患者的Th17、Treg、IL-23、IL-17水平,以Person系数检验急性胰腺炎患者Th17/Treg细胞平衡与IL-23/IL-17炎症轴的相关性。结果 与对照组相比,观察组Th17水平、Th17/Treg值较低,Treg、IL-23、IL-17水平较高(P<0.05);Th17、IL-23、IL-17水平及Th17/Treg值比较,MAPMSAP>SAP (P<0.0...     

Th17细胞与大疱性类天疱疮相关性研究

大疱性类天疱疮(bullous pemphigoid, BP)是一种获得性自身免疫性皮肤病,好发于老年人.既往研究认为BP为Th2细胞占优势的自身免疫性疾病.随着研究的深入,Th17细胞已成为研究的热点.其在防御胞外细菌感染、介导慢性炎症以及自身免疫病中发挥重要作用[1].白介素(IL)-23是T细胞分泌IL-17的关键触发因素,调节T细胞亚群分泌IL-17或IL-17相关细胞因子,形成IL-23/IL-17免疫应答途径.此途径在慢性肠病、自身免疫性疾病、肿瘤、变态反应性疾病等研究中已见到,而在自身免疫性大疱性皮肤病研究中却很少见到.为研究IL-17/IL-23免疫途径在BP发病中的作用机制及与临床的相关性,我们设计了本课题.     

寻常型银屑病患者Th17细胞及相关细胞因子的检测

目的:检测寻常型银屑病患者外周血Th17 细胞及相关细胞因子水平.方法:采用流式细胞分析法检测35 例寻常型银屑病患者和健康对照组外周血Th17 细胞,并分析与CD4+T 细胞比值;ELISA 法检测外周血IL-17 、IL-23 水平.结果:银屑病患者组外周血Th17/CD4+T 细胞比值为4.73% ± 0.78%,显著高于对照组2.52% ± 0.37%,差异有统计学意义(P＜0.01) ;银屑病患者外周血IL-17 和IL-23 水平亦明显高于对照组(P＜0.01).患者外周血IL-17 水平与IL-23 水平呈正相关(P＜0.01).结论:Th17 细胞可能参与了寻常型银屑病的发生与发展.     

Th17细胞在皮肤病的研究进展

Th17细胞不同于Th1、Th2细胞.它由记忆CD4+T细胞、初始T细胞等在IL-6和转化生长因子β、IL-1β或IL-23的作用下分化而来的.成熟的Th17细胞分泌IL-17、IL-22等多种细胞因子,在自身免疫疾病、宿主防御、炎症、肿瘤、移植物排斥等多种病理过程中起着重要的作用.概述Th17细胞的分化、相关细胞因子,以及在皮肤病发病机制中的作用.

Abstract：

Th17 cells are different from Th1 and Th2 cells. They are differentiated from memory CD4+T cells and naive T cells induced by interleukin (IL)-6, transforming growth factor (TGF) 3, IL-1β or IL-23.Mature Th17 cells can secrete many cytokines, such as IL-17, IL-22, etc, and play a crucial role in the pathological process of autoimmune diseases, host defense, inflammatory diseases, tumors and graft-versus-host diseases. This review presents the differentiation and related cytokines of Th17 cells as well as their roles in the pathogenesis of skin diseases.     

Th17细胞及其与银屑病关系的研究

Th17细胞是近来发现的一类新的CD4+T细胞亚群,具有与Th1、Th2不同的分化途径,分泌IL-17A/F等细胞因子, 对于该细胞生物学特性的研究有助于深入认识机体免疫调节规律,理解某些疾病发病机制,为寻找有效治疗靶点提供新的思路.本文就Th17细胞及其与银屑病的关系作一综述.     

阿维A对寻常型银屑病皮肤组织中Th1、Th17细胞的影响

采用免疫荧光双重标记法检测健康对照、阿维A治疗前、后寻常型银屑病患者皮损中Th1细胞(CD3+IFN-γ+)和Th17细胞(CD3+IL-17+)的数量变化.阿维A治疗前的寻常型银屑病患者皮损真皮浅层T细胞数量、Th1细胞数量、Th17细胞数量较健康对照组T细胞、Th1细胞、Th17细胞明显增多(P＜0.01);治疗后较治疗前皮损真皮浅层T细胞、Th1细胞、Th17细胞数明显下降(P＜0.01).阿维A治疗寻常型银屑病的作用可能涉及到其对Th1和Th17细胞的影响;同Th1细胞一样,Th17细胞可能是寻常型银屑病病情演变过程中关键的T细胞亚群之一.     

慢性特发性荨麻疹患者外周血调节性T细胞和IL-17水平的研究

慢性特发性荨麻疹(CIU)在临床很常见,其病因和发病机制尚不清楚.免疫因素在CIU的发病机制中起着重要作用,约30%的CIU发病以自身免疫机制为基础.Th17细胞和CD4+CD25+调节性T细胞亚群是近来发现的两类T细胞亚群.研究表明,这两类T细胞亚群和两者之间的失衡与多种自身免疫性疾病和皮肤病发病密切相关.IL-17可能在多种既往被认为是Th1或Th2介导的过敏性疾病中起作用[1].我们对CIU患者外周血调节性T细胞和IL-17水平进行研究.     

IL-23/Th17相关细胞因子在基底细胞癌中的表达水平及意义

目的探讨IL-23/Th17相关细胞因子在基底细胞癌(BCC)疾病进展中的作用。方法采用免疫组织化学染色的方法检测35例BCC组织及10例正常皮肤组织中IL-17、IL-22及IL-23的表达水平。结果IL-17在基底细胞癌中的表达水平高于正常皮肤组织(P<0.05),IL-17在基底细胞癌组织细胞和肿瘤间质细胞胞质中均有表达。IL-23在基底细胞癌中的表达水平高于正常皮肤组织(P<0.05),IL-23主要在基底细胞癌组织细胞胞质表达,部分位于肿瘤间质细胞胞质中。IL-22在基底细胞癌和正常皮肤组织的表达水平差异无统计学意义(P>0.05)。基底细胞癌中IL-17和IL-23的表达水平呈正相关(P<0.05)。结论IL-23/Th17相关细胞因子可能参与基底细胞癌的发生、发展。IL-23可能通过诱导Th17细胞的发育和增殖,促进IL-17分泌并在基底细胞癌的发生、发展中发挥协同作用。     

调节性T淋巴细胞和Th17细胞与银屑病的研究进展

银屑病是一种与T淋巴细胞相关的自身免疫性疾病,新近研究发现,除了与Th1细胞有关外,调节性T淋巴细胞尤其叉头/翅膀状螺旋转录因子诱导表达的调节性T细胞和Th17细胞在银屑病的发病过程中起着非常重要的作用。其中,叉头/翅膀状螺旋转录因子（＋）调节性T细胞平衡免疫抑制和免疫激活的转换在银屑病加重方面起到关键作用,Th17细胞分泌的细胞因子IL-17A、IL-17F、IL-22、IL-23、IL-36及肿瘤坏死因子α等在皮肤疾病发生发展中起到重要的作用。银屑病是由调节性T细胞和Th17细胞等多种免疫细胞和细胞因子共同参与的疾病。     

IL-17 and IL-17R: an auspicious therapeutic target for psoriatic disease

The continuous discovery of new T cell subpopulations in human autoimmune diseases is making the immunopathological network more complex. Th17 cells are one such newly identified subset of T cells, characterized by the production of signature cytokine IL-17. In last few years, several studies have strongly established the regulatory role of Th17 cells and its signature cytokine IL-17 in autoimmune diseases including psoriasis, psoriatic arthritis, rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus and multiple sclerosis. Psoriasis and PsA are immune mediated hyperproliferative diseases, affecting skin and joint respectively. Before the discovery of Th17 cells, psoriasis and psoriatic diseases were thought to be chiefly Th1 mediated diseases; later on IL-17 knockout animal studies as well as human experimental data indicate the crucial role of Th17 cells and its signature cytokine IL-17 in the pathogenesis of these diseases. In vitro human studies have shown the abundance of Th17 cells in the psoriatic plaques. Subsequently our research group has extended this observation in psoriatic arthritis and found the abundance of CD4+IL-17+ T cells in the synovial fluid and majority of these T cells are of memory phenotype (CD4RO+CD45RA-CD11a+). In addition, we showed the significant presence of functional IL-17 receptor in synovial fibroblast of psoriatic arthritis patients. Considering the strong association of IL-17 and psoriatic disease, IL-17 targeted therapy have shown promises in preclinical and clinical trials. In this review article, we have discussed the pathogenic role of IL-17 in psoriatic disease and summarized the therapeutic efficacy and safety profile of different anti IL-17 therapy as an anti-psoriatic agent.     

Th17细胞／Treg细胞及其失衡在慢性自发性荨麻疹发病机制中的作用

慢性自发性荨麻疹是一种常见的皮肤黏膜变态反应性疾病,以反复出现风团或红斑伴剧烈瘙痒为特征。介导免疫耐受的CD4＋CD25调节性T细胞和介导炎症反应的Thl7细胞是两类不同的CD4q＇细胞。两者数量此消彼长,功能拮抗,调节性T细胞和Thl7细胞数量和功能的平衡对维持免疫稳态起重要作用,失衡可引起免疫应答异常,导致包括慢性自发性荨麻疹在内的自身免疫性疾病的发生。初始CD4＋T细胞的细胞因子对他们之间的关系起到调节作用。     

白细胞介素-23/白细胞介素-17轴与自身免疫性皮肤病的研究进展

白细胞介素（IL）-23/IL-17轴是近年来新发现的炎性通路,主要依靠IL-23介导Th17效应细胞,产生IL-17等细胞因子,引起炎性反应及异常免疫,参与多种炎症及自身免疫性疾病.随着医学研究的不断进步,人们对IL-23/IL-17轴及其相关细胞、细胞因子,如Th17细胞、IL-23及IL-17等有了更加清晰的认识,并对其作用及机制有了进一步的了解.在越来越多的自身免疫性皮肤病中发现了此轴的参与.重点阐述了此轴在4种常见结缔组织病、寻常型天疱疮及坏疽性脓皮病中发挥的不同作用,针对此轴的治疗可能为这些自身免疫性皮肤病提供新的治疗靶向.     

性传播疾病与Thl7细胞关系的研究进展

Thl7细胞是近年来发现的一种不同于Thl、Th2细胞的CD4＋效应性T细胞亚群,以分泌IL-17为特点。Thl7细胞与梅毒、淋病及艾滋病的发病机制具有一定的相关性。Thl7细胞数目在梅毒螺旋体及淋球菌感染者体内存在变化,但Thl7细胞是否有利于梅毒及淋病的病情控制尚有争议。HIV感染者存在外周血Thl7和Treg细胞的不平衡,Thl7细胞比例较低,机体自发地控制病毒进展,需要保持Thl7／Treg的平衡,而Thl7细胞水平升高有利于控制病情。     

Role of IL-17 and IL-22 in autoimmunity and cancer

The dysregulation of inflammatory cytokines can cause a variety of diseases, such as autoimmunity and cancer. Since their identification in 2005, Th17 cells and its signature cytokine IL-17, have been implicated in the pathogenesis of autoimmune diseases such as psoriasis and rheumatoid arthritis (RA), and inflammatory associated cancers such as colorectal carcinoma (CRC). Recently, IL-22 a Th17 related cytokine has been shown to be pathogenic in psoriasis and RA. In this review, we will summarize the biological functions of IL-17 and IL-22, their role in autoimmune diseases and briefly review results from clinical trials targeting IL-17 or its receptor for the treatment of autoimmune diseases. Next, we will discuss pre-clinical and clinical data supporting the rationale of targeting other cytokines implicated in the Th17/IL-17 pathway, such as IL-22 and IL-23. Finally, we discuss the role of IL-17, and in particularly IL-22 in tumour immunity and possible therapeutic interventions.     

特应性皮炎与Th17的研究进展

特应性皮炎是一种慢性复发性、炎症性皮肤疾病,病因复杂,涉及环境、基因及免疫之间的相互作用,其中免疫因素为特应性皮炎发病的重要原因之一。Th17作为一个不同于Th1和2的CD4＋T细胞亚群,已经证实,在特应性皮炎发生发展中起重要的作用。Th17通过分泌白介素-17、21、22等细胞因子诱发炎症反应及免疫反应,参与特应性皮炎发病的免疫学机制。通过物理治疗、药物治疗等手段,可以靶向抑制Th17及相关细胞因子,对治疗特应性皮炎有一定疗效。     

SCID MOUSE MODEL OF PSORIASIS: A UNIQUE TOOL FOR DRUG DEVELOPMENT OF AUTOREACTIVE T-CELL AND TH-17 CELL-MEDIATED AUTOIMMUNE DISEASES

In both skin and synovial tissues of psoriatic arthritis (PsA) patients, there are prominent lymphocytic infiltrates localized to the dermal papillae in the skin and the sublining layer stroma in the joint. T-cells, with a predominance of CD4+ lymphocytes, are the most significant lymphocytes in the tissues; in contrast, this ratio is reversed in the epidermis, synovial fluid compartment, and at the enthesis, where CD8+ T-cells are more common. This differential tropism of CD8+ T-cell suggests that the CD8+ T-cells may be driving the immune response in the joint and skin. This is supported by an association with MHC class I. The cytokine network in the psoriatic skin and synovium is dominated by monocyte and T-cell-derived cytokines: IL-1β, IL-2, IL-10, IFN-γ, and TNF-α. In PsA synovium, higher levels of IFN-γ, IL-2, and IL-10 have been detected than in psoriatic skin. An analysis of T-cell receptor beta-chain variable (TCRβV) gene repertoires revealed common expansions in both skin and synovial inflammatory sites, suggesting an important role for cognate T-cell responses in the pathogenesis of PsA and that the inciting antigen may be identical or homologous between the afflicted skin and synovium. Traditionally, T-cells have been classified as T helper 1 (Th1) or Th2 cells by production of defining cytokines, IFN-γ and IL-4, respectively. Recently, a new type of T-cell, Th17, has been linked to autoimmune inflammation. T-helper 17 (Th17) cells are a unique effector CD4+ T-cell subset characterized by the production of interleukin (IL)-17. Murine diseases that were previously considered to be pure Th1-mediated responses have been shown to contain mixed populations of Th1 and Th17 cells. Also, in humans, a critical immunoregulatory role of Th-17 cells in infectious and autoimmune diseases has been identified. It has been postulated that IL-17 may be important in psoriasis. Our initial observations demonstrate that IL-17 and its receptor system are important for PsA also. In in vivo and in vitro studies we have demonstrated that IL-17/IL-17R are enriched in skin, synovial tissue, and synovial fluid of psoriatic arthritis patients and Th17 cells are functionally significant in the pathogenesis of psoriasis and psoriatic arthritis. Here we will share our experience of the SCID mouse model of psoriasis in respect to its use in investigating psoriatic diseases and development of immune-based drugs for psoriasis, psoriatic arthritis, and other autoimmune diseases.     

特应性皮炎患者外周血辅助性T细胞17与白介素17的检测

目的 探讨特应性皮炎（atopic dermatitis,AD）患者外周血白介素17蛋白和mRNA水平及辅助性T细胞17（Th17）表达及其意义。方法 用酶联免疫吸附测定法（ELISA）检测63例AD患者及30例正常人对照血浆中IL-17蛋白水平。实时荧光定量RT-PCR检测两组外周血中IL-17 mRNA表达水平。流式细胞仪检测AD患者和对照者外周血单一核细胞中Thl7细胞的比例。分析外周血Th17细胞比例和IL-17水平与AD患者病情严重度的相关性。结果 急性期AD患者外周血中Th17细胞比例为1.83% ± 0.47%,明显高于正常人对照组（0.85％ ± 0.45％,t = 4.128,P < 0.01）和慢性期组（1.12% ± 0.69%,t = 2.439,P < 0.05）。AD组外周血中血浆IL-17水平为98.37 ng/L,高于正常人组63.75 ng/L,U = 168,P < 0.05。AD组外周血IL-17mRNA表达水平高于正常人对照组。AD患者外周血Th17细胞比例和血IL-17蛋白水平与湿疹面积及严重度指数（EASI）积分均呈显著正相关（r = 0.68l,P < 0.01;r = 0.427,P < 0.05）。结论　急性期AD患者外周血Th17细胞比例显著升高, IL-17蛋白分泌及基因表达水平存在异常,与病情严重度明显相关,提示IL-17和Th17细胞可能在AD发病中起作用。     

Immunopathogenesis and role of T cells in psoriasis

Psoriasis is a T cell–dependent autoimmune disease of the skin and joints. Disease manifestation is orchestrated by proinflammatory CD4-positive T helper cells producing either interferon-γ (Th1) or interleukin (IL)-17 (Th17). These Th1 and Th17 cells interact with dermal dendritic cells, macrophages, mast cells, and neutrophils. Together, they cause an inflammation that mainly involves interferon-γ, tumor necrosis factor, IL-8, IL-12, IL-17, IL-19, and IL-23. New therapeutics either are directed against T cells, tumor necrosis factor, and IL-12/IL-23 or deviate immune responses into a protective IL-4–dominated Th2 phenotype.