Ⅱ型固有淋巴细胞及其在支气管哮喘中的作用

Ⅱ型固有淋巴细胞(ILC2s)是新近发现的一类固有免疫细胞群,在上皮细胞源性细胞因子白细胞介素(IL)-25、IL-33、胸腺基质淋巴细胞生成素(TSLP)及脂质递质等的刺激下可产生IL-5、IL-13等Th2型细胞因子,促进气道嗜酸粒细胞性炎症的发生。近年来,对于ILC2s介导的2型免疫应答在哮喘发病过程中作用方面所取得的研究取得了重大突破。本文就ILC2s及其在哮喘中的作用进行综述。     

2型固有淋巴细胞在蠕虫感染中的作用研究进展

蠕虫感染会诱发宿主产生固有及特异性免疫应答。2型固有淋巴细胞（group 2 innate lymphoid cells,ILC2）是2型免疫反应的重要参与者,在白细胞介素25(interleukin 25,IL-25)、IL-33和胸腺基质淋巴细胞生成素（thymic stromal lymphopoietin,TSLP）刺激下而产生大量辅助型T细胞2(T helper 2 cell, Th2)型细胞因子,从而在清除寄生虫及组织修复中发挥重要作用。近年来研究发现,蠕虫感染后,ILC2自分泌因子、肥大细胞、肠道神经系统、Th2细胞等均参与ILC2调控。探索ILC2在抗蠕虫免疫中发挥的作用极具基础研究与临床药物开发价值。本文就ILC2及其在蠕虫感染中的作用进行综述。     

2型固有淋巴细胞在过敏性疾病发生中的作用

过敏性疾病尤其是支气管哮喘(简称哮喘)一直被认为是由Th2细胞介导的炎症反应.近期研究发现,2型固有淋巴细胞(type-2 innate lymphoid cell,ILC2)作为一种先天性免疫细胞,同样参与哮喘发生的始动环节.该细胞可产生Th2型细胞因子IL-13、IL-5从而应答受损上皮组织释放的IL-33及IL-25,不仅仅作用于固有免疫的初级阶段,还介导获得性免疫相关功能,这使得先天性及获得性两种免疫系统之间存在了某种特殊的联系,也给研究过敏性哮喘发生机制带来了新的思路.     

3型固有淋巴细胞在炎症性肠病中的研究进展

炎症性肠病(IBD)是一种慢性非特异性肠道炎性疾病,其发病机制尚未完全明确.固有淋巴细胞(ILC)是近年来被发现的具有适应性免疫功能的固有免疫细胞,其中ILC3主要分布于肠黏膜固有层,并与其他免疫细胞、非造血细胞和肠道菌群作用形成动态网络,在肠道免疫防御和肠道屏障维持中起着重要作用.该文就ILC3在维持肠道稳态及IBD...     

气道上皮屏障功能异常在支气管哮喘发病中的作用

支气管哮喘(哮喘)的主要表现为咳嗽、咳痰、胸闷和喘息,这些症状的病理生理学基础是气道高反应性和气道慢性嗜酸粒细胞炎症。气道上皮细胞是呼吸道的第一道防线,环境因素和炎症作用的影响引起气道上皮反复损伤、修复和再生导致气道黏膜上皮的组织学改变和功能异常。气道上皮的屏障功能与气道上皮细胞因子胸腺基质淋巴细胞生成素,白细胞介素25和白细胞介素33密切相关,哮喘患者气道上皮屏障的损害增强了气道上皮黏膜对异物的通透性,引起气道上皮细胞、树突状细胞和先天性固有淋巴样细胞(ILC2s)的激活。气道上皮细胞的功能异常以及树突状细胞、Th2细胞和ILC2s的激活形成一个免疫病理单元,引起过敏性气道炎症,在哮喘的发病中发挥重要作用。     

白介素17与支气管哮喘气道炎症的研究进展

支气管哮喘(简称哮喘)是一种慢性呼吸道炎症性疾病,这种疾病在免疫病理学、临床表型、对治疗的反应、自然史方面存在异型却是越来越明显.曾经被视为纯粹的辅助性T细胞(Th)2型淋巴细胞、免疫球蛋白E、肥大细胞、嗜酸粒细胞、巨噬细胞和细胞因子主导的过敏性疾病,疾病还涉及局部上皮细胞、间质、血管、神经系统指挥的Th2细胞表型,以及通过异常损伤修复机制的气道壁重塑.近年发现IL-17在哮喘免疫过程起着重要作用,本文就哮喘气道炎症与IL-17研究进展综述如下.     

miR-155对变应性鼻炎患者ILC2转录因子GATA3调控作用的研究进展

［摘要］　Ⅱ型固有免疫细胞(ILC2)受刺激后可产生Th2型细胞因子,促进变应性鼻炎（AR）迟发相反应。miR-155在免疫系统的发育、免疫细胞的成熟分化以及维持免疫功能中都发挥至关重要的作用。GATA结合蛋白3（GATA3）是能够促进ILC2发育成熟的转录因子,而在肿瘤研究中,GATA3是miR-155的靶基因。该文对参与AR鼻黏膜中的ILC2转录因子GATA3及可干扰其表达的miR-155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。     

支气管哮喘病因和发病机制的研究进展

目前认为Th1/Th2型免疫应答失衡,是支气管哮喘(简称哮喘)发病的一个重要的免疫学机制.最近研究发现,哮喘的发病机制与许多因素有关.综述如下:吸烟是哮喘发病的危险因素之一.Th17及相关的细胞因子在哮喘中起着重要的作用.IL-33在哮喘的发病机制中起到重要的介导作用.MicroRNA的主要功能是在转录后水平调节相关基因表达,进而对机体生长、发育以及疾病发生过程调控.骨形成蛋白参与多种组织的纤维化进程,Gremlin是一种骨形成蛋白拮抗剂,探讨其在哮喘中的分布及作用,为哮喘发病机制的研究及治疗提供新的思路.脂肪细胞型脂肪酸结合蛋白在哮喘中发挥重要作用.     

Ⅱ型固有淋巴细胞在哮喘发病机制及治疗中的研究进展

<正>固有淋巴细胞(innate lymphoid cell,ILC)是与适应性免疫细胞平行的一类新型的细胞,此种细胞在组织修复、组织重塑以及固有免疫应答中具有重要的作用。ILC是起源于共同的前提细胞,虽然具有淋巴细胞的典型形态,但是没有重新排列的抗原受体。近年来,有关学者研究发现Ⅱ型固有淋巴细胞(type-2 innate lymphoid cell,ILC2)是ILC的一个     

Airway innate lymphoid cells in the induction and regulation of allergy

The recent discovery of innate lymphoid cells has revolutionized our understanding of the pathogenesis of immune diseases including allergy and asthma. Innate lymphoid cells (ILCs) are a heterogeneous collection of lymphocytes that lack antigen-specificity (non-T, non-B cells) and potently produce characteristic cytokines of T cell subsets (Th1, Th2, Th17). ILCs are divided into group 1 (ILC1s), group 2 (ILC2s), or group 3 (ILC3s). Similar to Th2 cells, ILC2s produce IL-4, IL-5, and IL-13, among others, and are present in increased numbers in samples from patients with many allergic disorders including asthma and chronic rhinosinusitis (CRS). Animal models have identified that ILC2s contribute to eosinophilic tissue infiltration, airway hyperresponsiveness, mucus production, as well as coordinate adaptive immune responses. Finally, recent studies support regulation of ILC2s by neuro-immune mechanisms as well as demonstrate a significant degree of plasticity between ILC subsets that may impact the immune responses in asthma and allergic airway diseases. Here, we review the current literature on ILC2s in human asthma and allergic airway diseases, as well as highlight some recent mechanistic insights into ILC2 function from in vitro studies and in vivo animal models.     

Insights into Group 2 Innate Lymphoid Cells in Human Airway Disease

Recent discoveries have led to the identification of a novel group of immune cells, the innate lymphoid cells (ILCs). The members of this group are divided into three subpopulations: ILC1s, ILC2s, and ILC3s. ILC2s produce Th2 cytokines, IL-4, IL-5, and IL-13, upon activation by epithelial cell-derived cytokines, lipid mediators (cysteinyl leukotrienes and prostaglandin D₂), and TNF family member TL1A and promote structural and immune cell responses in the airways after antigen exposure. In addition, ILC2 function is also influenced by inducible T cell costimulator (ICOS)/ICOS-ligand (ICOS-L) interactions via direct contact between immune cells. The most common airway antigens are allergens and viruses which are highly linked to the induction of airway diseases with underlying type 2 inflammation including asthma and allergic rhinitis. Based on recent findings linking ILC2s and airway Th2 responses, there is intensive investigation into the role of ILC2s in human disease with the hope of a better understanding of the pathophysiology and the discovery of novel potential therapeutic targets. This review summarizes the recent advances made in elucidating ILC2 involvement in human Th2 airway disease.     

Trained innate lymphoid cells in allergic diseases

Group 2 innate lymphoid cells (ILC2s) reside in peripheral tissues such as the lungs, skin, nasal cavity, and gut and provoke innate type 2 immunity against allergen exposure, parasitic worm infection, and respiratory virus infection by producing T_H2 cytokines. Recent advances in understanding ILC2 biology revealed that ILC2s can be trained by IL-33 or allergic inflammation, are long-lived, and mount memory-like type 2 immune responses to any other allergens afterwards. In contrast, IL-33, together with retinoic acid, induces IL-10-producing immunosuppressive ILC2s. In this review, we discuss how the allergic cytokine milieu and other immune cells direct the generation of trained ILC2s with immunostimulatory or immunosuppressive recall capability in allergic diseases and infections associated with type 2 immunity. The molecular mechanisms of trained immunity by ILCs and the physiological relevance of trained ILC2s are also discussed.     

Group 2 innate lymphoid cells in human asthma

Asthma is characterized by increased airway hyperresponsiveness, reversible airflow limitation, and remodeling due to allergic airway inflammation. Asthma has been proposed to be classified into various phenotypes by cluster analyses integrating clinical information and laboratory data. Recently, asthma has been classified into two major endotypes, Type 2-high and Type 2-low asthma, and various subtypes based on the underlying molecular mechanisms. In Type 2-high asthma, Th2 cells, together with group 2 innate lymphoid cells (ILC2s), produce type 2 cytokines such as IL-4, IL-5, IL-9, and IL-13, which play crucial roles in causing airway inflammation. The roles of ILC2s in asthma pathogenesis have been analyzed primarily in murine models, demonstrating their importance not only in IL-33- or papain-induced innate asthma models but also in house dust mite (HDM)- or ovalbumin (OVA)-induced acquired asthma models evoked in an antigen-specific manner. Recently, evidence regarding the roles of ILC2s in human asthma is also accumulating. This minireview summarizes the roles of ILC2s in asthma, emphasizing human studies.     

Type 2 Innate Lymphocytes in Allergic Airway Inflammation

CD4⁺ T helper-2 (Th2) cells, which produce a unique profile of IL-4, IL-5 and IL-13 pro-inflammatory cytokines, are thought to be central in the orchestration and amplification of allergic asthma. However, a novel non-T/non-B lymphoid cell population, named type 2 innate lymphocytes (ILC2s), that produces high amounts of IL-5 and IL-13 was recently discovered. Unlike Th2 cells, these ILC2s are not antigen-restricted and are activated by epithelial cell-derived cytokines IL-25 and IL-33. In this review, we will focus on recent studies, mainly involving allergen-based mouse models, that have provided evidence for a significant contribution of ILC2 to allergic airway information.     

Control of immunity and allergy by steroid hormones

Steroid hormones, especially glucocorticoids, androgens, and estrogens, have profound influence on immunity. Recent studies using cell-type specific steroid hormone receptor-deficient mice have revealed the precise roles of some of these hormones in the immune system. Glucocorticoids are known to have strong anti-inflammatory and immunosuppressive effects and pleiotropic effects on innate and adaptive immune responses. They suppress the production of inflammatory cytokines by macrophages and DCs and the production of IFN-γ by NK cells, thus inhibiting innate immunity. By contrast, glucocorticoids enhance the immune response by inducing the expression of IL-7R and CXCR4 in T cells and the accumulation of T cells in lymphoid organs in accordance with the diurnal change of the glucocorticoid concentration. Thus, glucocorticoids suppress innate immunity but enhance adaptive immunity. Androgens suppress the homeostasis and activation of ILC2s and the differentiation of Th2 and Th17 cells and enhance the suppressive function of Tregs, thereby alleviating allergic airway inflammation. Thus, these steroid hormones have pleiotropic functions in the immune system. Further investigations are awaited on the regulation of immunity and allergy by estrogens using cell-specific steroid hormone receptor-deficient mice.     

Role of airway epithelial barrier dysfunction in pathogenesis of asthma

Bronchial asthma is characterized by persistent cough, increased sputum, and repeated wheezing. The pathophysiology underlying these symptoms is the hyper-responsiveness of the airway along with chronic airway inflammation. Repeated injury, repair, and regeneration of the airway epithelium following exposure to environmental factors and inflammation results in histological changes and functional abnormalities in the airway mucosal epithelium; such changes are believed to have a significant association with the pathophysiology of asthma. Damage to the barrier functions of the airway epithelium enhances mucosal permeability of foreign substances in the airway epithelium of patients with asthma. Thus, epithelial barrier fragility is closely involved in releasing epithelial cytokines (e.g., TSLP, IL-25, and IL-33) because of the activation of airway epithelial cells, dendritic cells, and innate group 2 innate lymphoid cells (ILC2). Functional abnormalities of the airway epithelial cells along with the activation of dendritic cells, Th2 cells, and ILC2 form a single immunopathological unit that is considered to cause allergic airway inflammation. Here we use the latest published literature to discuss the potential pathological mechanisms regarding the onset and progressive severity of asthma with regard to the disruption of the airway epithelial function.