IL-4 drastically decreases deuterosomal and multiciliated cells via alteration in progenitor cell differentiation

Hyung Ju Cho, Youn Wook Chung, Sungmin Moon, Ju Hee Seo, Miran Kang, Jae Sung Nam, Sang Nam Lee, Chang Hoon Kim, Augustine M.K. Choi, Joo Heon Yoon

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Background: Allergic inflammation affects the epithelial cell populations resulting in goblet cell hyperplasia and decreased ciliated cells. Recent advances in single-cell RNA sequencing (scRNAseq) have enabled the identification of new cell subtypes and genomic features of single cells. In this study, we aimed to investigate the effect of allergic inflammation in nasal epithelial cell transcriptomes at the single-cell level. Methods: We performed scRNAseq in cultured primary human nasal epithelial (HNE) cells and in vivo nasal epithelium. The transcriptomic features and epithelial cell subtypes were determined under IL-4 stimulation, and cell-specific marker genes and proteins were identified. Results: We confirmed that cultured HNE cells were similar to in vivo epithelial cells through scRNAseq. Cell-specific marker genes were utilized to cluster the cell subtypes, and FOXJ1+-ciliated cells were sub-classified into multiciliated and deuterosomal cells. PLK4 and CDC20B were specific for deuterosomal cells, and SNTN, CPASL, and GSTA2 were specific for multiciliated cells. IL-4 altered the proportions of cell subtypes, resulting in a decrease in multiciliated cells and loss of deuterosomal cells. The trajectory analysis revealed deuterosomal cells as precursor cells of multiciliated cells and deuterosomal cells function as a bridge between club and multiciliated cells. A decrease in deuterosomal cell marker genes was observed in nasal tissue samples with type 2 inflammation. Conclusion: The effects of IL-4 appear to be mediated through the loss of the deuterosomal population, resulting in the reduction in multiciliated cells. This study also newly suggests cell-specific markers that might be pivotal for investigating respiratory inflammatory diseases.

Original languageEnglish (US)
Pages (from-to)1866-1877
Number of pages12
JournalAllergy: European Journal of Allergy and Clinical Immunology
Volume78
Issue number7
DOIs
StatePublished - Jul 2023

Keywords

  • IL-4
  • deuterosomal cells
  • epithelium
  • multiciliated cells
  • single-cell RNA sequencing

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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