Research ArticleALLERGY

Single-cell transcriptomic analysis of allergen-specific T cells in allergy and asthma

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Science Immunology  12 Jun 2020:
Vol. 5, Issue 48, eaba6087
DOI: 10.1126/sciimmunol.aba6087

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Finding a TRAIL to allergy control

House dust mites (HDMs) are a major source of aeroallergens that trigger human allergic responses including asthma. To characterize the heterogeneity of human CD4+ T helper (TH) cell responses to HDM antigens, Seumois et al. stimulated blood T cells with HDM peptides and isolated the freshly activated T cells for single-cell RNA sequencing. A TH subset expressing an interferon response gene signature (designated THIFNR) and the cell death–inducing TRAIL ligand was more frequent in individuals without HDM allergy. This TRAIL+ THIFNR subset may function to restrain allergic TH2 responses. Individuals with both HDM allergy and asthma were enriched for interleukin-9–producing TH2 cells. These findings provide a basis for designing more precise approaches to thwart pathogenic TH responses contributing to allergic asthma.

Abstract

CD4+ T helper (TH) cells and regulatory T (Treg) cells 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 nonasthmatics 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 individuals with HDM-reactive asthma. The number of interleukin-9 (IL-9)–expressing HDM-reactive TH cells is greater in asthmatics with HDM allergy compared with nonasthmatics with HDM allergy, and this IL-9–expressing TH subset displays 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, tumor necrosis factor–related apoptosis-inducing ligand, 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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