Single cell analysis of airways in allergic asthma with allergen profiling and spatial transcriptomics

Résumé fourni par la source

Inflammation in allergic asthma is driven by mast cell degranulation, which is a direct effect of IgE release by plasma cells when allergen is presented by TH2 cells. To better understand this process we conducted bronchoscopies on 4 people with allergic asthma and high titres of house dust mite specific IgE, and 4 healthy controls, analysing ~75,000 CD45+ cells from bronchoalveolar lavage, nasal brushes, and lung biopsies. We used immune repertoire sequencing and a custom protein-antibody conjugate to detect cells binding DerP1 and DerP2. We performed spatial transcriptomics (n=23) using 10X Xenium to characterise cellular niches in asthma. We identified 52 distinct cell states, observing minimal changes in cell abundance between health and asthma: primarily increased CD52+ macrophages expressing MHC class II antigen presentation. There were profound differences between airway tissue compartments. We identified differentially expressed genes linked to mediators of inflammation (TNF, interferon), hypoxia, and epithelial-mesenchymal transition, and steroid-induced gene signatures. We observed binding of IgE by mast cells, basophils, and type 2 dendritic cells in allergic asthma, with DerP1 binding to activated B cells but DerP2 to memory B cells. Spatial transcriptomics recapitulated these cell types and identified epithelial cell subsets, including submucosal glands. We characterised airway mucosal cell interaction niches (epithelial, immune, vascular) and profiled their role in disease. In summary, we provided a comprehensive transcriptional profile and tissue abundance of innate and antigen specific immune cells in allergic asthma.

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