Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Front Immunol. 2023 Jun 12;14:1149203. doi: 10.3389/fimmu.2023.1149203. eCollection 2023.
Prosperous advances in understanding the cellular and molecular mechanisms of chronic inflammation and airway remodeling in asthma have been made over the past several decades. Asthma is a chronic inflammatory disease of the airways characterized by reversible airway obstruction that is self-resolving or remits with treatment. Around half of asthma patients are "Type-2-high" asthma with overexpression of type 2 inflammatory pathways and elevated type 2 cytokines. When stimulated by allergens, airway epithelial cells secrete IL-25, IL-33, and TSLP to derive a Th2 immune response. First ILC2 followed by Th2 cells produces a series of cytokines such as IL-4, IL-5, and IL-13. T cells control IgE synthesis by secreting IL-4 to allergen-specific B cells. IL-5 promotes eosinophil inflammation, while IL-13 and IL-4 are involved in goblet cell metaplasia and bronchial hyperresponsiveness. Currently, "Type-2 low" asthma is defined as asthma with low levels of T2 biomarkers due to the lack of reliable biomarkers, which is associated with other Th cells. Th1 and Th17 are capable of producing cytokines that recruit neutrophils, such as IFN-γ and IL-17, to participate in the development of "Type-2-low" asthma. Precision medicine targeting Th cells and related cytokines is essential in the management of asthma aiming at the more appropriate patient selection and better treatment response. In this review, we sort out the pathogenesis of Th cells in asthma and summarize the therapeutic approaches involved as well as potential research directions.
在过去的几十年中，人们对哮喘中慢性炎症和气道重塑的细胞和分子机制的理解取得了繁荣的进展。哮喘是一种气道的慢性炎症性疾病，其特征是可逆性气道阻塞，可自行缓解或随治疗而缓解。大约一半的哮喘患者为“2 型高”哮喘，其 2 型炎症途径过度表达，2 型细胞因子升高。当受到过敏原刺激时，气道上皮细胞分泌 IL-25、IL-33 和 TSLP，以引发 2 型免疫反应。首先是 ILC2，然后是 Th2 细胞产生一系列细胞因子，如 IL-4、IL-5 和 IL-13。T 细胞通过分泌 IL-4 来控制过敏原特异性 B 细胞的 IgE 合成。IL-5 促进嗜酸性粒细胞炎症，而 IL-13 和 IL-4 参与杯状细胞化生和支气管高反应性。目前，“2 型低”哮喘定义为 T2 生物标志物水平低的哮喘，这是由于缺乏可靠的生物标志物，与其他 Th 细胞有关。Th1 和 Th17 能够产生招募中性粒细胞的细胞因子，如 IFN-γ 和 IL-17，参与“2 型低”哮喘的发展。针对 Th 细胞及其相关细胞因子的精准医学在哮喘管理中至关重要，旨在更适当地选择患者并获得更好的治疗反应。在这篇综述中，我们梳理了哮喘中 Th 细胞的发病机制，并总结了相关的治疗方法及潜在的研究方向。
