减毒活菌卡介苗对哮喘小鼠气道炎症及外周血Th1/Th2平衡的影响

诸多研究表明，辅助T细胞(Th2)占优势的Th1／Th2失衡是哮喘发病的重要机制。减毒活菌卡介苗(BCG)是一很强的Th1型细胞诱导剂，本研究意在观察BCG对小鼠哮喘模型气道炎症及外周血Th1／Th2平衡的影响。     

CpG DNA对支气管哮喘Th1/Th2类细胞因子调节的研究进展

支气管哮喘（哮喘）发病的重要基础是辅助性T细胞（T helper cell，Th）两种亚型Th1和Th2细胞组成的比例及功能失衡。CpG DNA能抑制嗜酸粒细胞（eosinophils，EOS）的气道浸润，抑制气道变应性炎症，使Th2型细胞因子白介素4（IL-4）产生减少，并诱导Th1型细胞因子白介素12（IL-12）和7干扰素（IFN-γ）产生，诱导Th1反应，下调Th2反应，使Th2反应向Thl反应转变，进而使Th1／Th2细胞比例和功能达到平衡的状态，在哮喘治疗中具有重要的意义。     

白介素-12治疗支气管哮喘的研究进展

支气管哮喘（哮喘）是一种气道慢性炎症性疾病，具有较高的发病率和病死率。作为Thl型细胞因子，IL-12能促进Th0向Thl分化，抑制Th2型炎症反应。大量的动物实验已经证实，IL-12无论单独应用还是作为免疫佐剂，均可逆转哮喘动物体内Th2／Th1失衡和抑制气道变态反应性炎症。同时，IL-12基因治疗在动物实验中也显示了哮喘治疗作用。虽然临床研究显示外源性IL-12治疗哮喘会伴有严重细胞因子毒性作用，但随着用药方式的更新，IL-12可能会成为新一代的抗哮喘药物。     

细胞因子与过敏性哮喘

支气管哮喘是一种慢性气道炎症性疾病。在气道炎症反应中，无论是Th2型细胞因子（IL-4、IL-5、IL-13等），还是Th1型细胞因子IFN-γ均起着重要作用。新近研究进一步表明调节性T细胞（Treg）产生的细胞因子也与过敏性哮喘的发病密切相关。     

鼠白细胞介素12基因治疗对支气管哮喘小鼠CD44和CD49d表达的影响

白细胞介素12（IL-12）能促进Th1细胞分化，抑制Th2细胞分化，纠正支气管哮喘（简称哮喘）发病中的Th1／Th2失衡。但长期体内直接应用IL-12重组蛋白可引起严重的不良反应。因此将IL-12基因以质粒为载体导人体内，使之产生内源性的IL-12而达到抑制炎症的作用，在哮喘的防治中具有一定的理论和实际意义。小鼠IL-12质粒（mIL-12质粒）对哮喘气道炎症和细胞因子的影响研究已经获得初步结果，     

CpG ODN的免疫调节作用及其在支气管哮喘中的应用

CpG ODN是含有CpG基序的脱氧寡核苷酸,它具有强大的免疫调节作用,能够激活自然杀伤细胞（NK）、单核／巨噬细胞、树突状细胞（DC）、B细胞和T细胞等多种免疫细胞,诱导并增强非特异性及特异性免疫应答;同时还可以诱导产生Th1型免疫反应,下调Th2型反应,调控免疫应答类型。在支气管哮喘（哮喘）动物模型研究中发现,CpG ODN能够有效地抑制气道炎症、气道高反应性及气道重构的发生和发展,在预防和治疗哮喘方面具有广阔的应用前景。     

信号转导子和转录激活子6、过氧化物酶体增殖，活化体受体-γ与支气管哮喘

Th1／Th2细胞比例失调和Th2细胞优势分化是支气管哮喘发病的主要机制。信号转导子和转录激活子6（STAT6）是Th2细胞特异性转录因子，被IL-4等激活后诱导相关炎症基因的表达：STAT6信号通路在支气管哮喘气道炎症和高反应性中起重要作用。过氧化物酶体增殖活化体受体-γ（PPAR-γ）可通过抑制炎症信号通路，减轻气道炎症并抑制气道重构等。本文综述了STAT6在哮喘炎症中的作用及PPAR-γ对支气管哮喘炎症等方面的影响，为哮喘的临床治疗提供新的思路。     

调节性T细胞与支气管哮喘的研究进展

支气管哮喘(简称哮喘)是一种慢性气道炎症性疾病,尤以机体Th2型免疫反应为主要表现,而近年来的大量研究表明调节性T细胞具有抑制Th2型反应的功能。通过对哮喘患者体内的调节性T细胞进行干预,来达到对哮喘的治疗和预防作用,已成为目前哮喘领域研究的热点。     

调节性T细胞与支气管哮喘的研究进展

支气管哮喘(简称哮喘)是一种慢性气道炎症性疾病,尤以机体Th2型免疫反应为主要表现,而近年来的大量研究表明调节性T细胞具有抑制Th2型反应的功能.通过对哮喘患者体内的调节性T细胞进行干预,来达到对哮喘的治疗和预防作用,已成为且前哮喘领域研究的热点.     

过敏性支气管哮喘免疫发病机制的最新研究进展

过敏性支气管哮喘(简称哮喘)是一种由不同的辅助性T细胞亚型决定的慢性气道炎症性疾病.既往认为“Th2哮喘假说”是过敏性哮喘的主要发病机制,而越来越多的研究表明,除了Th2之外其他辅助性T细胞也参与了哮喘的发病机制,尤其是Th1和Th17细胞对于气道中性粒细胞型炎症的发展至关重要.抑制这些免疫细胞也许为过敏性哮喘的有效治疗提供了方向.     

Protective T cell immunity against respiratory syncytial virus is efficiently induced by recombinant BCG

Respiratory syncytial virus (RSV) is one of the leading causes of childhood hospitalization and a major health burden worldwide. Unfortunately, because of an inefficient immunological memory, RSV infection provides limited immune protection against reinfection. Furthermore, RSV can induce an inadequate Th2-type immune response that causes severe respiratory tract inflammation and obstruction. It is thought that effective RSV clearance requires the induction of balanced Th1-type immunity, involving the activation of IFN-γ-secreting cytotoxic T cells. A recognized inducer of Th1 immunity is Mycobacterium bovis bacillus Calmette–Guérin (BCG), which has been used in newborns for decades in several countries as a tuberculosis vaccine. Here, we show that immunization with recombinant BCG strains expressing RSV antigens promotes protective Th1-type immunity against RSV in mice. Activation of RSV-specific T cells producing IFN-γ and IL-2 was efficiently obtained after immunization with recombinant BCG. This type of T cell immunity was protective against RSV challenge and caused a significant reduction of inflammatory cell infiltration in the airways. Furthermore, mice immunized with recombinant BCG showed no weight loss and reduced lung viral loads. These data strongly support recombinant BCG as an efficient vaccine against RSV because of its capacity to promote protective Th1 immunity.     

白介素-13和哮喘发病的研究进展

支气管哮喘（简称哮喘）是一种严重威胁人类健康的慢性呼吸道疾病。在世界范围内,过敏性哮喘的发病率和病死率逐年上升。研究表明,哮喘的发病是由于Th2型细胞过度释放细胞因子后诱导IgE产生,导致肥大细胞和嗜酸粒细胞脱颗粒,引起气道速发性过敏反应和以嗜酸粒细胞、肥大细胞、T细胞等多种炎症细胞参与的慢性气道炎症。白介素-13（IL-13）是一种由CD4^＋、Th2型细胞分泌的多效性细胞因子,介导变态反应的发生,与哮喘的发生有密切的关联。     

CpG的信号传递机制及其在支气管哮喘等过敏性疾病的应用

支气管哮喘在全球范围特别是发达国家的发病率迅速增加.这被认为与患者幼年时期没有充分暴露在细菌或细菌产物环境下而导致过敏易感性增加有关.CpG-脱氧核苷酸是模拟细菌DNA的合成核苷酸链,可以通过Toll样受体(TLR)被细胞识别,并通过TLR/核因子κB(NF-κB)途径和MAPK途径等诱导Th1型细胞反应,下调Th2型细胞反应,调节免疫应答类型.动物实验证实其可以有效抑制哮喘模型的气道炎症、气道高反应性和气道重塑等,在临床实验中亦已开展诸多研究,因此有关CpG及其作用机制的研究可能成为支气管哮喘治疗的新突破口.     

The interplay between neuroendocrine activity and psychological stress-induced exacerbation of allergic asthma

Psychological stress is recognized as a key factor in the exacerbation of allergic asthma, whereby brain responses to stress act as immunomodulators for asthma. In particular, stress-induced enhanced type 2 T-helper (Th2)-type lung inflammation is strongly associated with asthma pathogenesis. Psychological stress leads to eosinophilic airway inflammation through activation of the hypothalamic-pituitary-adrenal pathway and autonomic nervous system. This is followed by the secretion of stress hormones into the blood, including glucocorticoids, epinephrine, and norepinephrine, which enhance Th2 and type 17 T-helper (Th17)-type asthma profiles in humans and rodents. Recent evidence has shown that a defect of the μ-opioid receptor in the brain along with a defect of the peripheral glucocorticoid receptor signaling completely disrupted stress-induced airway inflammation in mice. This suggests that the stress response facilitates events in the central nervous and endocrine systems, thus exacerbating asthma. In this review, we outline the recent findings on the interplay between stress and neuroendocrine activities followed by stress-induced enhanced Th2 and Th17 immune responses and attenuated regulatory T (Treg) cell responses that are closely linked with asthma exacerbation. We will place a special focus on our own data that has emphasized the continuity from central sensing of psychological stress to enhanced eosinophilic airway inflammation. The mechanism that modulates psychological stress-induced exacerbation of allergic asthma through neuroendocrine activities is thought to involve a series of consecutive pathological events from the brain to the lung, which implies there to be a “neuropsychiatry phenotype” in asthma.     

Interaction of environmental allergens with airway epithelium as a key component of asthma

Epithelial cells in the airway wall actively interact with environmental antigens/allergens, both in healthy individuals and patients with asthma. In patients with (allergic) asthma, the epithelium is abnormal, showing damaged structures and continuous activation similar to a repair phenotype cell. Epithelial cells bind allergens by a diversity of innate receptors, similar and in part identical to the Toll-like receptor family, which can induce the release of cytokines, chemokines, and growth factors. Protease-containing extracts (house dust mite, fungi) may additionally cause damage of the epithelial cell layer, thereby enhancing the repair phenotype of epithelial cells in patients with asthma. These interactions may result in facilitation of transport of allergens and enhanced presentation to the immune system (Th2-type response). The inflammatory response induces a second phase of Th2-type cytokines and cytotoxic products that will enhance growth factor-mediated airway remodeling, as is found in asthma. An understanding of the largely unknown innate responses of epithelial cells with environmental antigens/allergens may open new treatment modalities for asthma and other airway diseases.     

白介素13与支气管哮喘的研究进展

支气管哮喘是以Th2型细胞因子增高和气道高反应性为特征的变态反应性疾病。白介素13是一种由CD4＋Th2型细胞分泌的多效性细胞因子,它通过诱导B细胞增殖和分化,促进IgE合成,活化嗜酸粒细胞,抑制嗜酸粒细胞的凋亡,诱导气道高反应性等机制,在支气管哮喘的发生、发展中起重要作用。     

白介素13与支气管哮喘的研究进展

支气管哮喘是以Th2型细胞因子增高和气道高反应性为特征的变态反应性疾病.白介素13是一种由CD4+ Th2型细胞分泌的多效性细胞因子,它通过诱导B细胞增殖和分化,促进IgE合成,活化嗜酸粒细胞,抑制嗜酸粒细胞的凋亡,诱导气道高反应性等机制,在支气管哮喘的发生、发展中起重要作用.     

Rhinovirus-induced lower respiratory illness is increased in asthma and related to virus load and Th1/2 cytokine and IL-10 production

Acute exacerbations are the major cause of asthma morbidity, mortality, and health-care costs and are difficult to treat and prevent. The majority of asthma exacerbations are associated with rhinovirus (RV) infection, but evidence supporting a causal relationship is weak and mechanisms are poorly understood. We hypothesized that in asthmatic, but not normal, subjects RV infection would induce clinical, physiologic, and pathologic lower airway responses typical of an asthma exacerbation and that these changes would be related to virus replication and impaired T helper 1 (Th1)/IL-10 or augmented Th2 immune responses. We investigated physiologic, virologic, and immunopathologic responses to experimental RV infection in blood, induced sputum, and bronchial lavage in 10 asthmatic and 15 normal volunteers. RV infection induced significantly greater lower respiratory symptoms and lung function impairment and increases in bronchial hyperreactivity and eosinophilic lower airway inflammation in asthmatic compared with normal subjects. In asthmatic, but not normal, subjects virus load was significantly related to lower respiratory symptoms, bronchial hyperreactivity, and reductions in blood total and CD8⁺ lymphocytes; lung function impairment was significantly related to neutrophilic and eosinophilic lower airway inflammation. The same virologic and clinical outcomes were strongly related to deficient IFN-γ and IL-10 responses and to augmented IL-4, IL-5, and IL-13 responses. This study demonstrates increased RV-induced clinical illness severity in asthmatic compared with normal subjects, provides evidence of strong relationships between virus load, lower airway virus-induced inflammation and asthma exacerbation severity, and indicates augmented Th2 or impaired Th1 or IL-10 immunity are likely important mechanisms.     

CpG-寡核苷酸与支气管哮喘

Th1／Th2失衡是支气管哮喘的重要免疫学发病机制,近年在支气管哮喘的发病机制中取得较大进展,CD4^＋T辅助细胞按其分泌的细胞因子不同分为Th1和Th2细胞,Th1反应可以抑制Th2反应,抑制气遭慢性炎症,含有未甲基化CpG结构的寡核苷酸是近年研究较多的一种调节Th1／Th2平衡的免疫制剂,本文就其调节Th1／Th2平衡在支气管哮喘治疗中的应用前景作一综述。