Single-cell transcriptomic analysis reveals key immune cell phenotypes in the lungs of patients with asthma exacerbation
Single-cell transcriptomic analysis reveals key immune cell phenotypes in the lungs of patients with asthma exacerbation
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单细胞转录组分析揭示哮喘急性发作患者肺部的关键免疫细胞表型
DOI：
10.1016/j.jaci.2020.09.032
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发表时间：
2021-03-04
影响因子：
14.2
通讯作者：
Zhang, Guojun
中科院分区：
文献类型：
--
作者：
Li, Hui;Wang, Huaqi;Zhang, Guojun
背景：哮喘急性发作与哮喘症状加重有关，严重者可导致住院治疗。然而，分子免疫过程中，确定的过程中的恶化仍然知之甚少，阻碍了有效的therapeutis.Objective的发展：我们的目的是确定候选基因，是强烈相关的哮喘急性发作在一个cellular level.Methods：哮喘急性发作和健康对照组的受试者被招募，和支气管肺泡灌洗液分离这些受试者通过支气管镜检查。通过荧光激活细胞分选法分离细胞，并对富集的细胞群体进行单细胞RNA测序。结果：我们发现，患者支气管肺泡灌洗液中单核细胞、CD 8（+）T细胞和巨噬细胞的水平显著升高。一组细胞因子和细胞内转导调节因子与哮喘急性发作相关，并且在多个细胞簇中共享，形成复杂的分子框架。另外一组核心加重相关模块被激活，包括真核起始因子2信号传导、肝配蛋白受体信号传导和CD 8（+）T细胞亚群（C1-a）和单核细胞簇中的C-X-C趋化因子受体4型信号传导（C7簇），这与感染有关。我们的研究确定了大量的严重哮喘相关基因，这些基因在多个细胞簇中差异表达。
Background: Asthma exacerbations are associated with heightened asthma symptoms, which can result in hospitalization in severe cases. However, the molecular immunologic processes that determine the course of an exacerbation remain poorly understood, impeding the progression of development of effective therapies.Objective: Our aim was to identify candidate genes that are strongly associated with asthma exacerbation at a cellular level.Methods: Subjects with asthma exacerbation and healthy control subjects were recruited, and bronchoalveolar lavage fluid was isolated from these subjects via bronchoscopy. Cells were isolated through fluorescence-activated cell sorting, and single-cell RNA sequencing was performed on enriched cell populations.Results: We showed that the levels of monocytes, CD8(+) T cells, and macrophages are significantly elevated in the bronchoalveolar lavage fluid of patients. A set of cytokines and intracellular transduction regulators are associated with asthma exacerbations and are shared across multiple cell clusters, forming a complicated molecular framework. An additional group of core exacerbation-associated modules is activated, including eukaryotic initiation factor 2 signaling, ephrin receptor signaling, and C-X-C chemokine receptor type 4 signaling in the subpopulations of CD8(+) T cells (C1-a) and monocyte clusters (C7 clusters), which are associated with infection.Conclusion: Our study identified a significant number of severe asthma-associated genes that are differentially expressed by multiple cell clusters.