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Single-cell transcriptomic analysis of allergen-specific T cells in allergy and asthma [scRNA-Seq]

ABSTRACT: CD4+ helper T cells (TH) and regulatory T cells (Treg) that respond to common allergens play an important role in driving and dampening airway inflammation in patients with asthma. Until recently, direct, unbiased molecular analysis of allergen-reactive TH and Treg cells has not been possible. To better understand the diversity of these T cell subsets in allergy and asthma, we analyzed the single-cell transcriptome of ~50,000 house dust mite (HDM) allergen-reactive TH cells and Treg cells from asthmatics with HDM allergy and from three control groups: asthmatics without HDM allergy and non-asthmatics with and without HDM allergy. Our analyses show that HDM allergen-reactive TH and Treg cells are highly heterogeneous, and certain subsets are quantitatively and qualitatively different in subjects with HDM-reactive asthma. The number of interleukin (IL)-9 expressing HDM-reactive TH cells is greater in asthmatics compared with non-asthmatics with HDM allergy, and display enhanced pathogenic properties. More HDM-reactive Th and Treg cells expressing the interferon-response signature (THIFNR and TregIFNR) are present in asthmatics without HDM allergy compared with those with HDM allergy. In cells from these subsets (THIFNR and TregIFNR), expression of TNFSF10 was enriched; its product, TRAIL, dampens activation of TH cells. These findings suggest that the THIFNR and TregIFNR subsets may dampen allergic responses, which may help explain why only some people develop TH2 responses to nearly ubiquitous allergens.

ORGANISM(S): Homo sapiens

PROVIDER: GSE146170 | GEO | 2020/06/10

REPOSITORIES: GEO

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Single-cell transcriptomic analysis of allergen-specific T cells in allergy and asthma [RNA-Seq]

Project description:CD4+ helper T cells (TH) and regulatory T cells (Treg) that respond to common allergens play an important role in driving and dampening airway inflammation in patients with asthma. Until recently, direct, unbiased molecular analysis of allergen-reactive TH and Treg cells has not been possible. To better understand the diversity of these T cell subsets in allergy and asthma, we analyzed the single-cell transcriptome of ~50,000 house dust mite (HDM) allergen-reactive TH cells and Treg cells from asthmatics with HDM allergy and from three control groups: asthmatics without HDM allergy and non-asthmatics with and without HDM allergy. Our analyses show that HDM allergen-reactive TH and Treg cells are highly heterogeneous, and certain subsets are quantitatively and qualitatively different in subjects with HDM-reactive asthma. The number of interleukin (IL)-9 expressing HDM-reactive TH cells is greater in asthmatics compared with non-asthmatics with HDM allergy, and display enhanced pathogenic properties. More HDM-reactive Th and Treg cells expressing the interferon-response signature (THIFNR and TregIFNR) are present in asthmatics without HDM allergy compared with those with HDM allergy. In cells from these subsets (THIFNR and TregIFNR), expression of TNFSF10 was enriched; its product, TRAIL, dampens activation of TH cells. These findings suggest that the THIFNR and TregIFNR subsets may dampen allergic responses, which may help explain why only some people develop TH2 responses to nearly ubiquitous allergens.

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