屋尘螨对T辅助细胞应答的单细胞RNA测序定义了气道Th2细胞独特基因表达信号
2019/08/28
摘要
幼稚CD4+ T细胞分化为功能多样的T辅助细胞亚群。Th2细胞在哮喘发病过程中起着重要作用，但其转录谱尚不清楚。我们在变应性气道疾病的屋尘螨(HDM)模型中，对来自淋巴结、肺和气道的T辅助细胞进行单细胞RNA测序(scRNA-seq)。scRNA-seq解析了幼稚CD4+ T、Th1、Th2、调节性T细胞(Treg)和CD4+ T细胞群对I型干扰素的转录谱。气道中Th2细胞被富集，可转录Cd200r1、IL6、Plac8、Igfbp7等多种基因，并通过染色质开放性分析和流式细胞术检测其mRNA谱。与脂质代谢相关的通路在Th2细胞中富集，关键代谢通路抑制剂的实验支持了葡萄糖和脂质代谢的作用。这些发现为了解致病性Th2细胞在过敏环境下的分化提供了线索。
Abstract
Naive CD4+ T cells differentiate into functionally diverse T helper (Th) cell subsets. Th2 cells play a pathogenic role in asthma, yet a clear picture of their transcriptional profile is lacking. We performed single-cell RNA sequencing (scRNA-seq) of T helper cells from lymph node, lung, and airways in the house dust mite (HDM) model of allergic airway disease. scRNA-seq resolved transcriptional profiles of naive CD4+ T, Th1, Th2, regulatory T (Treg) cells, and a CD4+ T cell population responsive to type I interferons. Th2 cells in the airways were enriched for transcription of many genes, including Cd200r1, Il6, Plac8, and Igfbp7, and their mRNA profile was supported by analysis of chromatin accessibility and flow cytometry. Pathways associated with lipid metabolism were enriched in Th2 cells, and experiments with inhibitors of key metabolic pathways supported roles for glucose and lipid metabolism. These findings provide insight into the differentiation of pathogenic Th2 cells in the context of allergy.
幼稚CD4+ T细胞分化为功能多样的T辅助细胞亚群。Th2细胞在哮喘发病过程中起着重要作用，但其转录谱尚不清楚。我们在变应性气道疾病的屋尘螨(HDM)模型中，对来自淋巴结、肺和气道的T辅助细胞进行单细胞RNA测序(scRNA-seq)。scRNA-seq解析了幼稚CD4+ T、Th1、Th2、调节性T细胞(Treg)和CD4+ T细胞群对I型干扰素的转录谱。气道中Th2细胞被富集，可转录Cd200r1、IL6、Plac8、Igfbp7等多种基因，并通过染色质开放性分析和流式细胞术检测其mRNA谱。与脂质代谢相关的通路在Th2细胞中富集，关键代谢通路抑制剂的实验支持了葡萄糖和脂质代谢的作用。这些发现为了解致病性Th2细胞在过敏环境下的分化提供了线索。
(中日友好医院呼吸与危重症医学科 张 清 摘译 林江涛 审校)
(Immunity. 2019 Jul 16;51(1):169-184.e5. doi: 10.1016/j.immuni.2019.05.014.)
(Immunity. 2019 Jul 16;51(1):169-184.e5. doi: 10.1016/j.immuni.2019.05.014.)
Single-Cell RNA Sequencing ofthe T Helper Cell Response to House Dust MitesDefines a Distinct Gene Expression Signature in Airway Th2 Cells.
Tibbitt CA, Stark JM, Martens L, Ma J, Mold JE, Deswarte K, Oliynyk G, Feng X, Lambrecht BN, De Bleser P, Nylén S, Hammad H, Arsenian Henriksson M, Saeys Y, Coquet JM.
Abstract
Naive CD4+ T cells differentiate into functionally diverse T helper (Th) cell subsets. Th2 cells play a pathogenic role in asthma, yet a clear picture of their transcriptional profile is lacking. We performed single-cell RNA sequencing (scRNA-seq) of T helper cells from lymph node, lung, and airways in the house dust mite (HDM) model of allergic airway disease. scRNA-seq resolved transcriptional profiles of naive CD4+ T, Th1, Th2, regulatory T (Treg) cells, and a CD4+ T cell population responsive to type I interferons. Th2 cells in the airways were enriched for transcription of many genes, including Cd200r1, Il6, Plac8, and Igfbp7, and their mRNA profile was supported by analysis of chromatin accessibility and flow cytometry. Pathways associated with lipid metabolism were enriched in Th2 cells, and experiments with inhibitors of key metabolic pathways supported roles for glucose and lipid metabolism. These findings provide insight into the differentiation of pathogenic Th2 cells in the context of allergy.
上一篇：
转胶蛋白-2在癌症和哮喘中的生化和临床意义
下一篇：
在重症哮喘患者中，嗜酸性粒细胞外网状陷阱通过刺激气道上皮活化2型固有淋巴细胞
