寻常型白癜风患者Th1、Th2及Th17部分相关细胞因子的研究

发布时间：2018-04-30 00:12

  本文选题：白癜风 + γ-干扰素　； 参考：《南方医科大学》2010年硕士论文

【摘要】： 白癜风是一种原发的、局限性或泛发性皮肤色素脱失症,是由于皮肤和毛囊的黑素细胞的酪氨酸酶系统的功能减退、丧失而引起的。白癜风可能是由于遗传素质和免疫因素联合作用所致的一种皮肤病,确切发病机制尚未完全阐明,最近研究表明：细胞免疫状态的改变、自身免疫和细胞因子在白癜风发病过程中起着重要的作用。 目前认为初始CD4+辅助T细胞可分为4种细胞亚群,分别是Th1、Th2、Th17和调节T细胞(Tregs)。免疫系统可分为天然免疫和适应性免疫两大部分,天然免疫系统可对外来的细菌、病毒及肿瘤细胞提供快速、非特异性的免疫效应。此外,天然免疫对决定适应性免疫应答的强度上也起着重要作用。天然免疫系统由抗原递呈细胞(APC)、单核巨噬细胞、树突状细胞(DCs)和NK细胞组成,而适应性免疫由辅助T淋巴细胞亚群组成,它可分为Th1和Th2,这两类免疫系统共同参与调节体内的免疫应答。Th1细胞主要分泌γ-干扰素(IFN-γ)、肿瘤坏死因子.-α(TNF-α)、白细胞介素-2(IL-2)、IL-12等细胞因子,主要介导细胞免疫；Th2细胞主要分泌IL-4、IL-5、IL-10、IL-13等细胞因子,主要介导体液免疫。正常情况下Th1/Th2处于相对平衡状态,不同疾病可引起Th1/Th2漂移,而Th1/Th2漂移又反过来影响疾病本身的进展。Th17细胞是-类新的CD4+T细胞亚群,这类细胞除了能特异性的分泌IL-17A和IL-17F,它还能产生IL-6、IL-1β、IL-22等细胞因子。上述这些细胞因子均有强大的致炎效应,在类风湿性关节炎、银屑病、炎症性肠病中Th17细胞均发挥着重要作用,除此之外,过敏性疾病和哮喘的发病也与Th17细胞密切相关。Th17细胞作为新的CD4+T效应T细胞亚群,具有独立的分化和发育机制,转化生长因子-β(TGF-β)和IL-6联合作用促进其分化,IL-23促进其增殖和存活,Th1和Th2细胞因子及IL-27则抑制其分化。孤独受体(RORγt)是控制其分化的转录因子。Th17细胞特异地产生的IL-17、IL-22等效应因子,主要介导炎症反应、自身免疫性疾病等的发生和发展。IL-12和IL-23共享IL-12p40亚单位,为证明IL-23在疾病中的作用,人们比较IL-12p35和IL-23p19亚单位基因敲除小鼠与自身免疫性疾病发生的关系,当IL-12p35基因敲除后,对自身免疫性疾病的发生无明显影响,而当IL-23p19基因敲除后,自身免疫性疾病的发生率明显降低,疾病的严重程度也明显减轻,同时Th17细胞减少,IL-17水平下降。调节T细胞为抑制性T细胞,是某些组成性表达CD25的CD4+T细胞。此类细胞可抑制性调节CD4+或CD8+T细胞活化与增殖,在免疫应答中发挥调节作用。目前认为,CD4+CD25+调节T细胞来源于胸腺,也可由成熟的CD4+CD25调节T细胞在外周淋巴组织中接触特异性抗原,或在免疫抑制因子作用下活化而形成,它具有免疫无能性和免疫抑制性两大特征,它可通过细胞之间直接接触的方式抑制其它效应性免疫细胞的功能,是迄今为止发现的最重要的免疫抑制细胞。 目的： 白癜风的发病与免疫机制密切相关,既往有学者对白癜风患者Th1和Th2细胞因子进行了研究,但结果并不一致,而对Th17细胞因子的研究,目前未见报道,故本研究从CD4+T细胞的三个细胞亚群Th1、Th2和Th17相关细胞因子入手进行分析,探讨寻常型白癜风患者的免疫状态及部分相关细胞因子在白癜风发病中的作用。 方法： 1.选取44例寻常型白癜风患者及40例健康对照,抽取外周血,分离血清采用ELISA方法检测白癜风患者和正常对照组外周血中IFN-γ、IL-10和IL-17的水平。 2.分离外周血中的单个核细胞,应用实时荧光定量PCR法对上述研究对象外周血单个核细胞的IL-17mRNA的相对含量进行检测。 3.统计分析：用SPSS13.0统计软件对所有试验数据进行统计分析,不同分期的寻常型白癜风患者之间以及不同临床类型的寻常型白癜风患者之间IFN-γ、IL-10、IL-17及IL-17mRNA水平的比较采用One-Way-ANOVA进行分析,计量资料采用均数±标准差表示,若方差齐,两两之间比较采用LSD法,若方差不齐,则采用近似F检验Welch法,两两比较则采用Dunnttt's T3法,各细胞因子的水平与疾病病程的相关性检验采用Pearson相关分析,均采用双侧检验,检验水准为α=0.05。 结果： 1. IFN-γ在不同分期、不同类型的患者之间均无显著性差异(F=1.568,1.950；P=0.215,0.110),与疾病的病程也无相关性(r=0.083,P=0.242)。 2.IL-10在不同分期、不同类型的白癜风患者中有显著性差异(F=38.884,17.906；P=0.000),基于方差分析的多种比较表明,IL-10在进展期显著高于稳定期,稳定期显著高于正常对照组。泛发性白癜风患者IL-10的水平显著高于正常对照组(P0.05),而局限性白癜风IL-10的水平与正常对照组相比无显著性差异(P0.05)。IL-10的水平与疾病的病程无相关性(r=0.090,P=0.126)。 3.IL-17在不同分期、不同类型的白癜风患者中有显著性差异(F=27.487,13.698；P=0.000),基于方差分析的多种比较表明,IL-17在进展期显著高于稳定期,稳定期显著高于正常对照组。泛发性白癜风患者IL-17的水平显著高于正常对照组(P0.05),而局限性白癜风IL-17的水平与正常对照组相比无显著性差异(P0.05),IL-17的水平与疾病的病程无相关性(r=0.215,P=0.276)。 4. IL-17mRNA在不同分期、不同类型的白癜风患者中有显著性差异(F=22.284,15.342；P=0.000),基于方差分析的多种比较表明,IL-17mRNA在进展期显著高于稳定期,稳定期显著高于正常对照组。泛发性白癜风患者IL-17mRNA的水平显著高于正常对照组(P0.05),而局限性白癜风IL-17mRNA的水平与正常对照组相比无显著性差异(P0.05)。IL-17mRNA的水平与疾病的病程无相关性(r=0.145,P=0.365)。 结论： 1 Th2型细胞因子IL-10在寻常型白癜风患者中显著高于正常对照组,且进展期显著高于稳定期,泛发性高于正常对照组,但正常对照组与局限性比较,无显著性差异,表明Th1/Th2在寻常型泛发性白癜风患者中存在失衡,Th2细胞因子水平占优势,IL-10可能参与了寻常型泛发性白癜风的发病过程,并与疾病进展有关。 2 Th17型细胞因子IL-17及IL-17mRNA的水平在寻常型白癜风患者中显著高于正常对照组,且进展期显著高于稳定期,泛发性高于正常对照组,但正常对照组与局限性比较,无显著性差异,表明IL-17可能参与了寻常型泛发性白癜风的发病过程,并与疾病进展有关。
[Abstract]:Vitiligo is a primary, localized or generalized dermatosis caused by the loss of the function of the tyrosinase system of the melanocytes of the skin and hair follicles. Vitiligo may be a skin skin disease caused by the combination of genetic and immune factors. The exact pathogenesis has not yet been fully elucidated. Studies have shown that changes in cellular immunity, autoimmune and cytokines play an important role in the pathogenesis of vitiligo.
It is believed that the initial CD4+ assisted T cells can be divided into 4 subgroups, namely, Th1, Th2, Th17 and T cells (Tregs). The immune system can be divided into two parts of natural and adaptive immunity. The natural immune system can provide fast and non specific immune effects to foreign bacteria, virus and tumor cells. In addition, the natural immune response is determined by natural immune system. It also plays an important role in the intensity of adaptive immune response. The natural immune system consists of antigen presenting cells (APC), mononuclear macrophages, dendritic cells (DCs) and NK cells. The adaptive immunity is composed of auxiliary T lymphocyte subsets, which can be divided into Th1 and Th2. These two kinds of immune systems participate in regulating the immune response.Th1 in the body. Cells mainly secrete interferon gamma (IFN- gamma), tumor necrosis factor. - alpha (TNF- alpha), interleukin -2 (IL-2), IL-12 and other cytokines, which mainly mediate cellular immunity; Th2 cells mainly secrete cytokines such as IL-4, IL-5, IL-10, IL-13 and other cytokines, mainly mediated by medium conductors. Under normal conditions, Th1/Th2 is in a relatively balanced state, and the different diseases can cause Th1/Th. 2 drifting, and the Th1/Th2 drift in turn affects the disease itself..Th17 cells are the new CD4+T cell subsets. In addition to the specific secretion of IL-17A and IL-17F, these cells can also produce cytokines such as IL-6, IL-1 beta, IL-22 and so on. These cytokines have strong inflammatory effects in rheumatoid arthritis, psoriasis, and inflammation. Th17 cells play an important role in symptomatic enteropathy. In addition to this, the pathogenesis of allergic diseases and asthma is also closely related to Th17 cells as a new CD4+T effect T cell subgroup, which has an independent differentiation and development mechanism. The combination of transforming growth factor beta (TGF- beta) and IL-6 promotes its differentiation, IL-23 promotes its proliferation and survival. Live, Th1 and Th2 cytokines and IL-27 inhibit their differentiation. The solitary receptor (ROR gamma T) is a specific transcription factor.Th17 cell that controls the differentiation of IL-17, IL-22 and other effects factors, which mainly mediate the occurrence of inflammatory reactions, autoimmune diseases, and the development of.IL-12 and IL-23 shared IL-12p40 subunits, in order to prove that IL-23 is in the disease. People compare the relationship between IL-12p35 and IL-23p19 subunit knockout mice with autoimmune diseases. When IL-12p35 knockout, there is no obvious effect on the occurrence of autoimmune diseases. When IL-23p19 knockout, the incidence of autoimmune diseases is significantly reduced, and the severity of the disease is significantly reduced, and Th 17 cells decrease and IL-17 level decreases. Regulating T cells as inhibitory T cells is a CD4+T cell that expresses CD25 in some constituent cells. This kind of cell can inhibit the activation and proliferation of CD4+ or CD8+T cells and play an regulatory role in the immune response. It is believed that CD4+CD25+ regulates T cells from the thymus and can also be regulated by mature CD4+CD25 for T fine. Cells are exposed to specific antigens in peripheral lymphoid tissue or activated by immunosuppressive agents. It has two major characteristics of immune incompetence and immunosuppression. It can inhibit the function of other effector cells through direct contact between cells. It is the most important immunosuppressive cell that has been found so far.
Objective:
The pathogenesis of vitiligo is closely related to the immune mechanism. Previous scholars have studied the Th1 and Th2 cytokines in vitiligo patients, but the results are not consistent, and the study of Th17 cytokine is not reported. Therefore, this study begins with the analysis of the three cell subgroups of CD4+T cells, Th1, Th2 and Th17 related cytokines. The immune status of vitiligo patients and the role of some related cytokines in the pathogenesis of vitiligo.
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