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Single-Cell RNA Sequencing of the T Helper Cell Response to House Dust Mites Defines a Distinct Gene Expression Signature in Airway Th2 Cells.
Immunity ( IF 25.5 ) Pub Date : 2019-06-20 , DOI: 10.1016/j.immuni.2019.05.014
Christopher Andrew Tibbitt 1 , Julian Mario Stark 1 , Liesbet Martens 2 , Junjie Ma 1 , Jeff Eron Mold 3 , Kim Deswarte 4 , Ganna Oliynyk 1 , Xiaogang Feng 1 , Bart Norbert Lambrecht 4 , Pieter De Bleser 2 , Susanne Nylén 1 , Hamida Hammad 4 , Marie Arsenian Henriksson 1 , Yvan Saeys 5 , Jonathan Marie Coquet 1
Affiliation  

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.

中文翻译:

T辅助细胞对屋尘螨的反应的单细胞RNA测序在气道Th2细胞中定义了不同的基因表达特征。

幼稚的CD4 + T细胞可分化为功能多样的T辅助(Th)细胞亚群。Th2细胞在哮喘中起着致病作用,但仍缺乏清晰的转录图谱。我们在过敏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辅助细胞进行了单细胞RNA测序(scRNA-seq)。scRNA-seq解析了天然CD4 + T,Th1,Th2,调节性T(Treg)细胞和对I型干扰素有反应的CD4 + T细胞群体的转录谱。气道中的Th2细胞富集许多基因的转录,包括Cd200r1,Il6,Plac8和Igfbp7,并且它们的mRNA谱得到了染色质可及性和流式细胞仪分析的支持。与脂质代谢有关的途径富含Th2细胞,关键代谢途径抑制剂的实验支持了葡萄糖和脂质代谢的作用。这些发现提供了变态反应中致病性Th2细胞分化的见解。
更新日期:2019-06-20
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