Single-cell RNA-seq analysis reveals novel cell-cell communication interactions responsive to house dust mite and subject to TET1 regulation in the lung 9322

Abstract Description Epigenetic regulator, Tet1, protects against house dust mite (HDM)-induced allergic airway inflammation. We previously showed this may partially be due to the regulation of several stress response pathways by Tet1 in the airway epithelium. However, responses to HDM and the contribution of Tet1 in other lung cell types are unknown. A murine model of HDM-induced lung inflammation was established in Tet1 knockout and littermate wildtype mice. Total lung cells, as well as EpCAM+ airway epithelial cells, were subject to 10X Genomics single-cell RNA-seq workflow. ScRNA-seq analysis was performed using Cell Ranger, scAlign, and Seurat. Cell types were labeled using scMCA and confirmed using known markers. After 20 cell types were identified, cell communication networks were constructed using CellChat. While B cells were the most abundant immune cell type, macrophages had the most differentially expressed genes following HDM challenges. Loss of Tet1 and HDM challenges led to similar changes in cell-cell communication networks. Specifically, we observed an increased cell communication probability between innate lymphoid cells and both eosinophils and neutrophils via the CD40lg-(Itgam+Itgb2) interaction. Overall, exposure to HDM leads to cell-type-specific transcriptional changes which influence cross-talk between cell types in the lung, and such responses are regulated by Tet1. Funding Sources Supported by NIH/NIAID R01AI141569-01A1; T32 HL007013 Topic Categories Immediate Hypersensitivity, Asthma, and Allergic Responses (HYP)