Wellcome Sanger Institute, Cambridge, UK.
Open Targets, Cambridge, UK.
Nat Med. 2019 Jul;25(7):1153-1163. doi: 10.1038/s41591-019-0468-5. Epub 2019 Jun 17.
Human lungs enable efficient gas exchange and form an interface with the environment, which depends on mucosal immunity for protection against infectious agents. Tightly controlled interactions between structural and immune cells are required to maintain lung homeostasis. Here, we use single-cell transcriptomics to chart the cellular landscape of upper and lower airways and lung parenchyma in healthy lungs, and lower airways in asthmatic lungs. We report location-dependent airway epithelial cell states and a novel subset of tissue-resident memory T cells. In the lower airways of patients with asthma, mucous cell hyperplasia is shown to stem from a novel mucous ciliated cell state, as well as goblet cell hyperplasia. We report the presence of pathogenic effector type 2 helper T cells (T2) in asthmatic lungs and find evidence for type 2 cytokines in maintaining the altered epithelial cell states. Unbiased analysis of cell-cell interactions identifies a shift from airway structural cell communication in healthy lungs to a T2-dominated interactome in asthmatic lungs.
人类的肺部能够实现高效的气体交换，并与环境形成界面，这依赖于黏膜免疫来抵御感染因子。为了保护肺部免受感染，结构细胞和免疫细胞之间需要进行严格控制的相互作用。在这里，我们使用单细胞转录组学来描绘健康肺部的上、下呼吸道和肺实质以及哮喘肺部的下呼吸道的细胞景观。我们报告了与位置相关的气道上皮细胞状态和一种新型的组织驻留记忆 T 细胞亚群。在哮喘患者的下呼吸道中，黏液细胞增生被证明源于一种新型的黏液纤毛细胞状态，以及杯状细胞增生。我们报告了在哮喘肺部中存在致病性效应型 2 辅助 T 细胞（T2），并发现 2 型细胞因子在维持改变的上皮细胞状态方面的证据。对细胞间相互作用的无偏分析表明，健康肺部的气道结构细胞通讯向哮喘肺部中以 T2 为主的相互作用网络发生转变。
