影响支气管哮喘Th1／Th2失衡的因素及治疗的新视点

支气管哮喘（简称哮喘）是由嗜酸粒细胞、肥大细胞和T细胞等多种炎性细胞参与的气道慢性炎症性疾病，其发病机制极为复杂，近来研究发现Th1／Th2失衡是哮喘免疫学发病机制中的一个重要环节，本文就Th1／Th2失衡与哮喘的关系，Th1／Th2平衡的调节及其在哮喘治疗中的价值作一综述。     

Th2细胞因子与支气管哮喘发病机制的研究进展

支气管哮喘(简称哮喘)是由多种细胞和细胞因子参与的肺部慢性炎症性疾病.发病机制尚未完全清楚.目前认为Th1/Th2反应失衡导致Th2细胞过度激活是其重要的免疫学机制之一.Th2细胞产生的多效性细胞因子白介素4(IL-4)、IL-5和IL-13在此过程中发挥巨大作用,与哮喘发病密切相关.     

金水宝胶囊对支气管哮喘患者几种免疫细胞因子的影响

支气管哮喘是一种慢性炎症性气道疾病,免疫因素在哮喘的发病过程中发挥重要作用。以往认为辅助性T淋巴细胞Th1/Th2比例失衡是哮喘发病的重要机制。近年发现了一种以产生IL-17为主要细胞因子的Th17细胞,在哮喘的发病机制中同样具有重要作用,IL-17对于中性粒细胞参与的支气管哮喘气道炎症、气道高反应、气道重塑均发挥重要作用,有可能成为治疗哮喘的有意义的靶目标[1-3]。对支气管     

支气管哮喘中Th1/Th2模型漂移的研究进展

近年来Th1/Th2模型漂移在支气管哮喘发病机制中的研究已成为热点之一。Th1占优势者感局限，预后良好；Th2占优势者感染扩散，预后不良。而哪种T辅助细胞占优势取决于多种因素。有利于Th2占优势的因素有树突状细胞、B7／CD28协同刺激信号、转录因子GATA－3等；有利于Th1占优势的因素有CD8^ T淋巴细胞，CpG DNA,白介素－12、Zn^2 、一氧化氮及一些基础营养素等。本文就以上各因素的研究进展作一综述。     

信号转导子和转录激活子与Th1/Th2平衡在支气管哮喘中的作用研究

支气管哮喘是慢性气道炎症性疾病.在其发生、发展中,胞外信号分子、信号转导、信号转导子和转录激活子3个环节调控着Th细胞的分化.而Th1/Th2细胞失衡.细胞因子分泌紊乱,使气道炎症持续存在,其中STAT4和STAT6起关键作用.本文就STAT4和STAT6调控Th细胞分化的机制及研究进展作一综述.     

影响支气管哮喘Th1/Th2失衡的因素及治疗的新视点

支气管哮喘(简称哮喘)是由嗜酸粒细胞、肥大细胞和T细胞等多种炎性细胞参与的气道慢性炎症性疾病,其发病机制极为复杂,近来研究发现Th1/Th2失衡是哮喘免疫学发病机制中的一个重要环节,本文就Th1/Th2失衡与哮喘的关系,Th1/Th2平衡的调节及其在哮喘治疗中的价值作一综述.     

Th2／Th17细胞群与支气管哮喘机制研究

支气管哮喘（简称哮喘）是一种由多种细胞（如嗜酸粒细胞、肥大细胞、T淋巴细胞、中性粒细胞和气道上皮细胞等）和细胞组分参与的气道慢性炎症性疾病。经典的Th1／Th2细胞失衡被认为是过敏性哮喘的主要发病机制,Th17／IL-17轴被证实与重症哮喘、激素抵抗型哮喘、以中性粒细胞浸润为主的哮喘有关。近年来研究发现,机体内存在一种不同于目前已知的Thl、Th2、Thl7、Th9等的新型CD4＋T细胞,被称为Th2／Th17双表型记忆性CD4＋T细胞群（简称Th2／Th17细胞群）。在哮喘发病机制的探讨中发现,Th2／Th17细胞群既能分泌Th2表型细胞因子IL-4、IL-5、IL-13,也可以分泌Th17型细胞因子IL-17、IL-8、IL-22等;且在不同的微环境下发生不一样的生物学效应,这显示了Th2／Th17细胞群可能在哮喘发生发展（特别是重症哮喘）及各亚型相互转化过程中起着决定性作用。现就Th2／Th17细胞群的生物学功能及其与哮喘的相关性进行如下综述。     

Th17/Treg在支气管哮喘发病机制中的作用及研究进展

Th17/Treg的提出突破了经典理论Th1/Th2失衡的局限性,IL-17、IL-10在支气管哮喘(简称哮喘)中的发生发展已经引起高度关注,然而基于它们之间在哮喘发病机制中缺乏深度和系统性,本文就Th17/Treg细胞及其它们的主要相关因子IL-17、IL-10、中性粒细胞与哮喘关系的研究进展作一简要综述.     

银杏内酯对老年哮喘患者外周血Th1/Th2型细胞因子的作用

目的探讨银杏内酯对老年哮喘患者外周血T淋巴细胞Th1/Th2型细胞因子的作用及其治疗哮喘的可能机制。方法采用流式细胞术检测25例健康体检者正常对照组和25例老年支气管哮喘急性发作期患者单个核细胞（PBMC）经银杏内酯干预后Th1型细胞因子（IFN-γ）和Th2型细胞因子（IL-4）水平及Th1/Th2比值变化。结果与正常组比较,哮喘组Th2型细胞因子（IL-4）水平显著增高（P〈0.01）,哮喘组Th1/Th2比值显著减低（P〈0.01）。哮喘组银杏内酯体外干预后Th2型细胞因子（IL-4）水平较干预前显著减低（P〈0.01）,Th1/Th2比值较较干预前显著增高（P〈0.01）。结论银杏内酯具有抑制哮喘Th2细胞亚群优势反应和调节免疫平衡的作用。     

Th17/Treg在支气管哮喘发病机制中的作用及研究进展

Th17/Treg的提出突破了经典理论Th1/Th2失衡的局限性,IL-17、IL-10在支气管哮喘(简称哮喘)中的发生发展已经引起高度关注,然而基于它们之间在哮喘发病机制中缺乏深度和系统性,本文就Th17/Treg细胞及其它们的主要相关因子IL-17、IL-10、中性粒细胞与哮喘关系的研究进展作一简要综述.     

参麦注射液对支气管哮喘患者Th1/Th2免疫平衡的影响研究

目的 探讨参麦注射液治疗支气管哮喘的临床疗效及对患者Th1/Th2免疫平衡的影响.方法 80例支气管哮喘患者,随机分为治疗组及对照组,两组患者给与相同的抗炎、平喘、扩张支气管治疗,治疗组另给参麦注射液每日1次,2周后观察两组患者临床疗效、外周血Th1、Th2细胞及白介素4(IL-4)、γ干扰素(IFN-γ)表达水平.结果 治疗组临床总有效率高于对照组,治疗组治疗后血清Th1升高,Th2降低,Th1/Th2升高,IL-4水平降低,IFN-γ水平升高,且与对照组相比,有显著差异(P<0.05).结论 参麦注射液能够改善支气管哮喘患者Th1/Th2免疫失衡及炎症介质表达,辅助治疗支气管哮喘的疗效显著.     

泛福舒对支气管哮喘急性发作患者Th1/Th2细胞平衡及临床症状的影响

目的探讨泛福舒对支气管哮喘急性发作患者Th1/Th2细胞平衡及临床症状的影响。方法将72例支气管哮喘急性发作患者采用随机数表法分为观察组与对照组,每组36例。对照组患者使用硫酸特布他林气雾剂联合布地奈德气雾剂治疗,观察组患者在此基础上使用泛福舒治疗,比较两组患者的干扰素-γ、白介素-4、免疫球蛋白水平,临床症状缓解时间及疗效。结果治疗后,观察组患者的干扰素-γ水平明显高于对照组(P0.01),而白介素-4水平显著低于对照组(P0.01);观察组患者的免疫球蛋白G、A及M水平均明显高于对照组(P0.01);观察组患者的呼吸困难、咳嗽、喘憋及哮鸣音缓解时间均显著短于对照组(P0.01);观察组患者的治疗有效率为94.44%,明显高于对照组的69.44%(P0.01)。结论泛福舒可有效调节支气管哮喘急性发作患者的Th1/Th2细胞平衡,提高免疫功能,进而缓解临床症状,增强肺功能,值得临床应用。     

Th1/Th2漂移与支气管哮喘的免疫治疗

Th1/Th2细胞在不同的细胞因子、抗原等因素的影响下，可发生Th1/Th2的转换，研究表明在支气管哮喘（哮喘）的发生机制中，Th2细胞分化明显增多，而Th1细胞数目减少。因此，促进Th1反应，抑制Th2反应的免疫治疗是治疗哮喘的重要部分。目前许多调节Th1/Th2失衡的免疫治疗方法已取得一些进展。     

Suppressor of cytokine signaling 3 (SOCS3) in Th2 cells evokes Th2 cytokines, IgE, and eosinophilia

Atopic dermatitis, allergic rhinitis, and bronchial asthma are allergic immune disorders characterized by a predominance of T helper 2 (Th2) cells, the resulting elevation of allergen-speci.c immunoglobulin E (IgE), and mast cell- and eosinophil-associated inflammation. The cytokine environment at the site of the initial antigen stimulation determines the direction of helper T-cell differentiation into Th1 or Th2 cells. Therefore, negative regulators of cytokine signaling, suppressors of cytokine signaling (SOCS) proteins, play an important role in Th2-mediated allergic responses through the control of the balance between Th1 and Th2 cells. SOCS3 and SOCS5 are predominantly expressed in Th2 and Th1 cells, respectively, and they reciprocally inhibit the Th1 and Th2 differentiation processes. In this article, we discuss the role of SOCS3 and SOCS5 proteins in atopic asthma and allergic conjunctivitis and explore the potential of SOCS proteins as targets for therapeutic strategies in allergic disorders.     

Assessment of the Th1/Th2 paradigm in whole blood in atopy and asthma. Increased IFN-gamma-producing CD8(+) T cells in asthma

Atopy is characterized by an immune system that is biased to T helper cell, type 2 (Th2) activation. This condition predisposes to asthma, a disease in which a Th2 activation was found in blood and lungs. However, most blood studies have considered purified cells, which might give an incomplete view of immune reactions. In this study, we assessed in whole blood cultures the Th1/Th2 paradigm in atopy and asthma. Sixty-nine subjects (31 atopic asthmatics, six nonatopic asthmatics, 13 atopic nonasthmatics, and 19 control subjects) were included in this study. Interleukin-4 (IL-4), interferon gamma (IFN-gamma), and IL-12 were assayed in stimulated whole blood culture supernatants by using a flow cytometer microsphere-based assay. Intracellular IL-4 and IFN-gamma were detected in T cells and CD8(+) T cells by flow cytometry. Atopy was characterized by a higher production of IL-4, which was correlated to total IgE levels, and by an impairment of the T-cell capacity to produce IFN-gamma. This impairment was correlated to the number of positive skin tests. In asthma, the overproduction of IL-4 was still found if atopy was present. Unexpectedly, an overproduction of IFN-gamma was found, which was related to an increased capacity of CD8(+) T cells to produce IFN-gamma. The number of IFN-gamma-producing CD8(+) T cells was related to asthma severity, to bronchial hyperresponsiveness, and to blood eosinophilia. In addition, this number was correlated to IL-12 production. These results show that in addition to the well-known Th2 inflammation in asthma, there are IFN-gamma-producing CD8(+) T cells in the blood, possibly controlled by IL-12.     

基于miRNA表达谱解析细粒棘球蚴病患者体内Th17/Treg失衡机制

目的　观察细粒棘球蚴病患者血清微小RNA（miRNA）表达水平、探讨miRNA对辅助性T 细胞17（Th17）/调节性T细胞（Treg）失衡的影响,以阐明细粒棘球蚴慢性感染并长期致病的机制。方法　提取细粒棘球蚴病患者与健康对照者血清总RNA,采用Illumina测序平台进行高通量测序。分别采用miRBase数据库和miRDeep2工具进行已知miRNA注释和新miRNA预测,并进行差异分析。采用miRanda软件和TargetScan软件分别预测差异表达miRNA靶基因后取交集,进行基因本体（GO）富集分析以及京都基因和基因组百科全书（KEGG）通路分析。在差异表达变化倍数居前20位的miRNA中,匹配可靶向决定Th17细胞和Treg细胞生成的关键转录因子（RORC和FOXP3）或重要调控通路（PI3K⁃Akt和mTOR通路）相关基因的miRNA。结果　细粒棘球蚴病患者与健康对照血清中共有53个差异表达miRNA,其中47个上调表达miRNA、6个下调表达miRNA。GO富集分析显示,差异表达miRNA功能涉及DNA转录翻译、细胞成分、细胞形态、神经发育及代谢分解等过程。KEGG富集分析显示,这些差异表达miRNA靶基因涉及的主要信号通路包括MAPK、PI3K⁃Akt、mTOR等信号通路。在差异表达变化倍数居前20位的miRNA中,有3个潜在靶向调控RORC的miRNA、15个潜在靶向PI3K⁃Akt、mTOR信号通路的miRNA。结论　细粒棘球蚴感染后可使患者血清miRNA表达谱出现明显改变,差异表达miRNA可能通过靶向Th17/Treg关键转录因子或PI3K⁃Akt、mTOR通路而导致Th17/Treg免疫失衡,进而利于细粒棘球蚴在宿主体内长期寄生并慢性致病。     

Human Th2 cells selectively express the orexigenic peptide, pro-melanin-concentrating hormone

Th1 and Th2 cells represent the two main functional subsets of CD4(+) T helper cell, and are defined by their cytokine expression. Human Th1 cells express IFNgamma, whilst Th2 cells express IL-4, IL-5, and IL-13. Th1 and Th2 cells have distinct immunological functions, and can drive different immunopathologies. Here, we show that in vitro-differentiated human Th2 cells highly selectively express the gene for pro-melanin-concentrating hormone (PMCH), using real-time RT-PCR, enzyme immunoassay, and Western blot analysis. PMCH encodes the prohormone, promelanin-concentrating hormone (PMCH), which is proteolytically processed to produce several peptides, including the orexigenic hormone melanin-concentrating hormone (MCH). PMCH expression by Th2 cells was activation responsive and increased throughout the 28-day differentiation in parallel with the expression of the Th2 cytokine genes. MCH immunoreactivity was detected in the differentiated Th2 but not Th1 cell culture supernatants after activation, and contained the entire PMCH protein, in addition to several smaller peptides. Human Th1 and Th2 cells were isolated by their expression of IFNgamma and CRTH2, respectively, and the ex vivo Th2 cells expressed PMCH upon activation, in contrast to the Th1 cells. Because Th2 cells are central to the pathogenesis of allergic diseases including asthma, expression of PMCH by activated Th2 cells in vivo may directly link allergic inflammation to energy homeostasis and may contribute to the association between asthma and obesity.