Viral RNA sensing in airway basal cells weakens later barrier formation in cell study

Double-stranded RNA sensing in airway basal cells can impair the epithelial barrier those cells go on to form, according to a laboratory study published in BMC Molecular and Cell Biology on 4 November 2026. The finding, reported by Shinichi Okamoto, Shuichiro Maruoka and colleagues with Yasuhiro Gon, points to a mechanism that may help explain why airway barriers remain vulnerable after encounters with viral RNA, although the work has not yet been validated in live viral infections.

The researchers stimulated undifferentiated normal human bronchial epithelial cells and VA10 cells, which function as basal cells, with polyinosinic:polycytidylic acid (poly I:C), a synthetic ligand for the Toll-like receptor 3 (TLR3) that mimics double-stranded viral RNA. The treated cells were then cultured at an air-liquid interface (ALI) to assess how the prior RNA exposure affected the integrity of the airway epithelial barrier they subsequently formed. Global gene expression analysis was performed alongside the barrier measurements.

Poly I:C stimulation significantly decreased transepithelial electrical resistance, a standard measure of barrier integrity, and reduced the expression of barrier-related genes. This barrier dysfunction was attenuated when the researchers silenced TLR3 or its downstream adaptor, TIR-domain-containing adapter-inducing interferon-β (TRIF), indicating that both molecules were required during the exposure window for the impairment to occur. Transcriptomic analysis revealed distinct gene-expression patterns at the two time points examined. At day 10, replicated microarray analysis showed increased expression of inflammation- and remodeling-associated genes. At day 3, an exploratory pooled analysis, with individual genes validated by RT-qPCR in separate, non-pooled wells, showed induction of interferon-stimulated genes together with reduced expression of genes required for epithelial differentiation and barrier formation.

The authors propose, as a hypothesis to be tested directly, that double-stranded RNA sensing during this early window redirects basal cell differentiation. In their conclusion, they state that these findings suggest a mechanism by which dsRNA sensing in airway basal cells may contribute to persistent barrier vulnerability. The team is explicit about the limits of the current evidence: the mechanism was observed in basal-cell models stimulated with a synthetic TLR3 ligand rather than actual viruses, and the day-3 transcriptional findings come from an exploratory pooled analysis. The researchers note that validation using live respiratory viruses, and in primary cells from multiple donors, is required before this mechanism can be extended to viral infections.

Subject of Research: How double-stranded RNA sensing in airway basal cells affects subsequent epithelial barrier formation via TLR3/TRIF

Article Title: Double-stranded RNA sensing in airway basal cells impairs subsequent epithelial barrier formation via TLR3/TRIF

Article References: Okamoto, S., Maruoka, S., Tsuya, K., Hikichi, M., Yamada, S., Kurosawa, Y., Kozu, Y., & Gon, Y. (2026). Double-stranded RNA sensing in airway basal cells impairs subsequent epithelial barrier formation via TLR3/TRIF. BMC Molecular and Cell Biology. https://doi.org/10.1186/s12860-026-00610-x

Image Credits: AI Generated

DOI: 10.1186/s12860-026-00610-x

Keywords: airway basal cells, epithelial barrier, double-stranded RNA, TLR3, TRIF, poly I:C, air-liquid interface, transepithelial electrical resistance, interferon-stimulated genes, bronchial epithelial cells, Double-stranded, sensing