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Immunity. 2019 Jul 16;51(1):169-184.e5. doi: 10.1016/j.immuni.2019.05.014. Epub 2019 Jun 20.

Single-Cell RNA Sequencing of the T Helper Cell Response to House Dust Mites Defines a Distinct Gene Expression Signature in Airway Th2 Cells.

Author information

1
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 65 Stockholm, Sweden.
2
Data Mining and Modeling for Biomedicine, VIB Center for Inflammation Research, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
3
Department of Cell and Molecular Biology, Karolinska Institutet, 171 65 Stockholm, Sweden.
4
VIB Center for Inflammation Research, Ghent, Belgium; Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.
5
Data Mining and Modeling for Biomedicine, VIB Center for Inflammation Research, Ghent, Belgium; Department of Applied Mathematics, Computer Science and Statistics, Ghent University, Ghent, Belgium.
6
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 65 Stockholm, Sweden. Electronic address: jonathan.coquet@ki.se.

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.

KEYWORDS:

ATAC-seq; T helper; Th2; asthma; house dust mite; interleukin; metabolism; single-cell RNA Sequencing

PMID:
31231035
DOI:
10.1016/j.immuni.2019.05.014
[Indexed for MEDLINE]

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