Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia.
Clin Exp Allergy. 2019 May;49(5):564-581. doi: 10.1111/cea.13374. Epub 2019 Apr 4.
Severe asthma in children is a debilitating condition that accounts for a disproportionately large health and economic burden of asthma. Reasons for the lack of a response to standard anti-inflammatory therapies remain enigmatic. Work in the last decade has shed new light on the heterogeneous nature of asthma, and the varied immunopathologies of severe disease, which are leading to new treatment approaches for the individual patient. However, most studies to date that explored the immune landscape of the inflamed lower airways have focused on adults. T cells are pivotal to the inception and persistence of inflammatory processes in the diseased lungs, despite a contemporary shift in focus to immune events at the epithelial barrier. This article outlines current knowledge on the types of T cells and related cell types that are implicated in severe asthma. The potential for environmental exposures and other inflammatory cues to condition the immune environment of the lung in early life to favour pathogenic T cells and steroid resistance is discussed. The contributions of T cells and their cytokines to inflammatory processes and treatment resistance are also considered, with an emphasis on new observations in children that argue against conventional type 1 and type 2 T cell paradigms. Finally, the ability for new technologies to revolutionize our understanding of T cells in severe childhood asthma, and to guide future treatment strategies that could mitigate this disease, is highlighted.
儿童重度哮喘是一种使人虚弱的疾病，它在哮喘的健康和经济负担方面占比不成比例。对标准抗炎治疗反应不足的原因仍然难以解释。过去十年的工作为哮喘的异质性以及重度疾病的各种免疫病理学提供了新的认识，从而为个体患者带来了新的治疗方法。然而，迄今为止，大多数探讨下呼吸道炎症免疫谱的研究都集中在成年人身上。尽管目前的研究重点已转移到上皮屏障的免疫事件上，但 T 细胞仍然是肺部炎症过程发生和持续的关键。本文概述了目前关于在重度哮喘中涉及的 T 细胞类型和相关细胞类型的知识。讨论了环境暴露和其他炎症信号如何在生命早期 Conditioning 肺部的免疫环境，以利于致病性 T 细胞和类固醇耐药性。还考虑了 T 细胞及其细胞因子对炎症过程和治疗抵抗的贡献，重点是新的观察结果表明儿童中存在传统的 1 型和 2 型 T 细胞范式。最后，强调了新技术能够彻底改变我们对重度儿童哮喘中 T 细胞的理解，并为减轻这种疾病的未来治疗策略提供指导。
