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Updated: May 28, 2026
Identification and Characterization of Immunogenic RNA Species in HDM Allergens that Modulate Eosinophilic Lung Inflammation
Published on: May 30, 2020
Single-nucleus RNA sequencing identifies conserved structural cell programs in allergic lung inflammation
Annamalai Govindhan1, Aakash Sur2, Koa Hosoki1
1Department of Medicine, Immunology, Allergy, and Rheumatology, Baylor College of Medicine, Houston, Tex.
Background:
Lung structural cells contribute to allergic airway inflammation; however, the lung cell type that mounts the most vigorous early transcriptional response to allergen exposure remains unclear. In this study, we used single-nucleus RNA sequencing to define early allergen-induced transcriptional programs across major lung structural cell populations.
Objective:
We sought to identify the lung structural cell type that exhibits a unique and robust transcriptional response following allergen challenge.
Methods:
Wild-type C57BL/6J mice were sensitized and challenged with cat dander extract. Lung tissues were collected 4 hours postchallenge to capture early transcriptional events and 72 hours to assess allergic inflammation. Single-nucleus RNA sequencing was performed on nuclei from frozen lung tissue. Transcript quantification, cell-type annotation, and differential gene expression analyses were conducted using Cell Ranger, CellTypist, iDEP, and gene set enrichment analysis.
Results:
Allergen challenge induced early transcriptional responses across lung structural cell populations. Capillary endothelial cells displayed the greatest number of unique allergen-induced genes and showed enrichment of transcriptional programs related to DNA damage, oxidative stress, and pathways associated with expansion of GATA-3+ TH2 cells and RorγT+ TH17 cells in allergen-challenged lungs. In contrast, ciliated epithelial cells, alveolar type 1 and type 2 cells, and club cells shared a largely conserved allergen-responsive transcriptional signature, with only a limited subset of subtype-specific genes linked to TH2/TH17-associated pathways.
Conclusions:
Capillary endothelial cells represent a dominant and early transcriptionally specialized responder to allergen exposure, characterized by coordinated activation of DNA damage/repair, oxidative stress, and TH2/TH17-associated inflammatory programs. These findings identify capillary endothelial cells as key regulators of early allergic airway inflammation and highlight them as potential therapeutic targets in asthma.
