人肺单细胞测序首次揭示健康人和哮喘患者中细胞状态差异
2019/09/09
摘要
人的肺与外界相接触并能进行有效的气体交换，而这都依赖于黏膜免疫保护机体免受有害物质的影响。肺部结构与免疫细胞的紧密调控的相互作用是维持肺部稳态的重要保证。这篇文章通过使用单细胞转录组学勾画了健康肺的上气道和下气道及肺部间质以及哮喘肺下气道的细胞构成蓝图。我们发现了位置依赖的气道上皮细胞状态和一种新的组织固有记忆T细胞亚群。在哮喘病人的下气道，粘液细胞来源于一种新的粘液纤毛细胞状态，悲壮细胞增生也是如此。我们报道了在哮喘肺中存在病例效应T辅助2型细胞，并且发现了在维持上皮细胞状态改变的2型细胞因子存在的证据。对细胞间相互作用的无偏倚分析表明，健康肺的气道结构中细胞间相互作用向受Th2调控的哮喘肺细胞的相互作用组转变。
Vieira Braga FA, Kar G, Berg M, Carpaij OA, Polanski K, Simon LM, Brouwer S, Gomes T, Hesse L, Jiang J, Fasouli ES, Efremova M, Vento-Tormo R, Talavera-López C, Jonker MR, Affleck K, Palit S, Strzelecka PM, Firth HV, Mahbubani KT, Cvejic A, Meyer KB, Saeb-Parsy K, Luinge M, Brandsma CA, Timens W, Angelidis I Strunz M, Koppelman GH, van Oosterhout AJ, Schiller HB, Theis FJ, van den Berge M, Nawijn MC, Teichmann SA.
Abstract
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 (TH2) 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 TH2-dominated interactome in asthmatic lungs.
人的肺与外界相接触并能进行有效的气体交换，而这都依赖于黏膜免疫保护机体免受有害物质的影响。肺部结构与免疫细胞的紧密调控的相互作用是维持肺部稳态的重要保证。这篇文章通过使用单细胞转录组学勾画了健康肺的上气道和下气道及肺部间质以及哮喘肺下气道的细胞构成蓝图。我们发现了位置依赖的气道上皮细胞状态和一种新的组织固有记忆T细胞亚群。在哮喘病人的下气道，粘液细胞来源于一种新的粘液纤毛细胞状态，悲壮细胞增生也是如此。我们报道了在哮喘肺中存在病例效应T辅助2型细胞，并且发现了在维持上皮细胞状态改变的2型细胞因子存在的证据。对细胞间相互作用的无偏倚分析表明，健康肺的气道结构中细胞间相互作用向受Th2调控的哮喘肺细胞的相互作用组转变。
(中日友好医院呼吸与危重症医学科 张清 摘译 林江涛 审校)
(Nat Med. 2019 Jul;25(7):1153-1163. doi: 10.1038/s41591-019-0468-5)
(Nat Med. 2019 Jul;25(7):1153-1163. doi: 10.1038/s41591-019-0468-5)
A cellular census of human lungs identifies novel cell states in health and in asthma.
Vieira Braga FA, Kar G, Berg M, Carpaij OA, Polanski K, Simon LM, Brouwer S, Gomes T, Hesse L, Jiang J, Fasouli ES, Efremova M, Vento-Tormo R, Talavera-López C, Jonker MR, Affleck K, Palit S, Strzelecka PM, Firth HV, Mahbubani KT, Cvejic A, Meyer KB, Saeb-Parsy K, Luinge M, Brandsma CA, Timens W, Angelidis I Strunz M, Koppelman GH, van Oosterhout AJ, Schiller HB, Theis FJ, van den Berge M, Nawijn MC, Teichmann SA.
Abstract
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 (TH2) 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 TH2-dominated interactome in asthmatic lungs.
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氯暴露通过固有淋巴细胞和cd11c介导的巨噬细胞加重哮喘炎症
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高中性粒细胞哮喘患者血清IgE、OCS依赖性和IL-17／22表达水平升高
