In this review, we highlight experiments conducted in our laboratories that have elucidated functional roles for CD4+ T-helper type-2 lymphocytes (TH 2 cells), their associated cytokines, and eosinophils in the regulation of hallmark features of allergic asthma. Notably, we consider the complexity of type-2 responses and studies that have explored integrated signaling among classical TH 2 cytokines (IL-4, IL-5, and IL-13), which together with CCL11 (eotaxin-1) regulate critical aspects of eosinophil recruitment, allergic inflammation, and airway hyper-responsiveness (AHR). Among our most important findings, we have provided evidence that the initiation of TH 2 responses is regulated by airway epithelial cell-derived factors, including TRAIL and MID1, which promote TH 2 cell development via STAT6-dependent pathways. Further, we highlight studies demonstrating that microRNAs are key regulators of allergic inflammation and potential targets for anti-inflammatory therapy. On the background of TH 2 inflammation, we have demonstrated that innate immune cells (notably, airway macrophages) play essential roles in the generation of steroid-resistant inflammation and AHR secondary to allergen- and pathogen-induced exacerbations. Our work clearly indicates that understanding the diversity and spatiotemporal role of the inflammatory response and its interactions with resident airway cells is critical to advancing knowledge on asthma pathogenesis and the development of new therapeutic approaches.

中文翻译：

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对TH 2反应和气道炎症进行建模，以了解调节哮喘发病机理的基本机制。

在这篇综述中，我们重点介绍了在实验室中进行的实验，这些实验阐明了CD4 + T辅助2型淋巴细胞（TH 2细胞），其相关的细胞因子和嗜酸性粒细胞在过敏性哮喘标志性特征调节中的功能作用。值得注意的是，我们认为2型反应的复杂性和研究了经典TH 2细胞因子（IL-4，IL-5和IL-13）之间的整合信号传导的研究，这些因子与CCL11（eotaxin-1）一起调节关键方面嗜酸性粒细胞募集，变态反应性炎症和气道高反应性（AHR）。在我们最重要的发现中，我们提供了证据，TH 2反应的启动受气道上皮细胞衍生因子（包括TRAIL和MID1）调节，这些因子通过STAT6依赖性途径促进TH 2细胞发育。进一步，我们重点研究表明微RNA是过敏性炎症的关键调节剂以及抗炎治疗的潜在靶标的研究。在TH 2炎症的背景下，我们证明了先天性免疫细胞（尤其是气道巨噬细胞）在类固醇抗药性炎症和继发于变应原和病原体诱发的AHR中起着至关重要的作用。我们的工作清楚地表明，了解炎症反应的多样性和时空作用及其与驻留气道细胞的相互作用对于增进有关哮喘发病机理的知识和开发新的治疗方法至关重要。我们已经证明，先天性免疫细胞（尤其是气道巨噬细胞）在类固醇抗药性炎症和继发于变应原和病原体诱发的AHR的产生中起重要作用。我们的工作清楚地表明，了解炎症反应的多样性和时空作用及其与驻留气道细胞的相互作用对于增进有关哮喘发病机理的知识和开发新的治疗方法至关重要。我们已经证明，先天性免疫细胞（尤其是气道巨噬细胞）在类固醇抗药性炎症和继发于变应原和病原体诱发的AHR的产生中起重要作用。我们的工作清楚地表明，了解炎症反应的多样性和时空作用及其与驻留气道细胞的相互作用对于增进有关哮喘发病机理的知识和开发新的治疗方法至关重要。