Multi-site single cell investigation of airway immune populations in allergic asthma with allergen profiling 4296

Description Asthma is a chronic, heterogenous disease of the airways. It includes allergic asthma, which is thought to be driven by mast cell degranulation in an IgE- and Th2-dependent fashion, but which nevertheless remains poorly characterised. To better understand the site-specific effects of inflammation in allergic asthma, we used single-cell transcriptomics to analyse ∼80,000 CD45+ cells obtained from bronchioalveolar lavages, nasal brushes, and lung biopsies from 4 controls and 4 allergic asthmatics with high titers of IgE against house dust mite proteins. We also utilised single-cell immune repertoire sequencing along with a custom protein-antibody conjugate to detect the cells binding DerP1 and DerP2, the proteins most commonly responsible for dust mite allergy. We found profound differences between the airway sampling sites. In CD4+ T cells, we identified differentially expressed genes linked to antigen presentation, mediators of inflammation (TNF, interferons), hypoxia, and fibrosis. We also identified clonal expansion of CD4+ T cell subsets in allergic asthma. In mast cells, we observed upregulation of genes involved in antigen processing and presentation, as well as specific binding of DerP2, but not DerP1 protein by these cells. Cell-cell interaction analysis indicated intricate cell networks that may underpin pathology. Our study provides insights into the site-specific cellular landscape of allergic asthma, with therapeutic implications. Funding Sources Supported by Medical Research Council (MRC) grant MR/R015708/1 and Kymab/Sanofi. Topic Categories Immediate Hypersensitivity, Asthma, and Allergic Responses (HYP)