Mucosal IL-36 is a defining feature of severe paediatric bronchiolitis
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
Rationale
Bronchiolitis is the commonest cause of hospital admission in children under the age of 1 year, most cases being due to respiratory syncytial virus (RSV) infection. The mechanisms causing infantile bronchiolitis are incompletely understood but include a deficient mucosal interferon response, neutrophilic inflammation and enhanced mucosal Type-2 responses.
Objectives
We sought to determine the mucosal immune processes associated with severe paediatric bronchiolitis.
Methods
We performed transcriptomic analyses on mucosal samples from infants hospitalized with Moderate (n = 48) and Severe (n = 40) bronchiolitis. Differential expression and regression analyses determined genes associated with different severity categories. Responses were modelled in vitro using air–liquid interface human nasal epithelial cell culture models.
Measurements and main results
We confirmed weakened interferon-associated signalling in severe RSV and non-RSV bronchiolitis but unexpectedly found elevated IL-36α (an IL-1 family cytokine implicated in chronic inflammatory diseases) early in infection. Conversely, IL36A was decreased in whole blood during severe RSV, suggesting that this association is unique to the mucosa. In human nasal epithelial cells grown in vitro under air–liquid interface we found IL-36α to be produced by epithelial cells during RSV infection and that its secretion is enhanced by neutrophils.
Conclusions
These findings implicate mucosal IL-36α as a dominant feature of severe paediatric bronchiolitis.
Bronchiolitis is the commonest cause of hospital admission in children under the age of 1 year, most cases being due to respiratory syncytial virus (RSV) infection. The mechanisms causing infantile bronchiolitis are incompletely understood but include a deficient mucosal interferon response, neutrophilic inflammation and enhanced mucosal Type-2 responses.
Objectives
We sought to determine the mucosal immune processes associated with severe paediatric bronchiolitis.
Methods
We performed transcriptomic analyses on mucosal samples from infants hospitalized with Moderate (n = 48) and Severe (n = 40) bronchiolitis. Differential expression and regression analyses determined genes associated with different severity categories. Responses were modelled in vitro using air–liquid interface human nasal epithelial cell culture models.
Measurements and main results
We confirmed weakened interferon-associated signalling in severe RSV and non-RSV bronchiolitis but unexpectedly found elevated IL-36α (an IL-1 family cytokine implicated in chronic inflammatory diseases) early in infection. Conversely, IL36A was decreased in whole blood during severe RSV, suggesting that this association is unique to the mucosa. In human nasal epithelial cells grown in vitro under air–liquid interface we found IL-36α to be produced by epithelial cells during RSV infection and that its secretion is enhanced by neutrophils.
Conclusions
These findings implicate mucosal IL-36α as a dominant feature of severe paediatric bronchiolitis.
Date Issued
2026-02-09
Date Acceptance
2026-01-29
Citation
Mucosal Immunology
ISSN
1933-0219
Publisher
Elsevier
Journal / Book Title
Mucosal Immunology
Copyright Statement
Copyright © 2026 Copyright Owner. This is the author’s accepted manuscript made available under a CC-BY licence in accordance with Imperial’s Research Publications Open Access policy (www.imperial.ac.uk/oa-policy)
License URL
Identifier
10.1016/j.mucimm.2026.01.012
Publication Status
Accepted
Date Publish Online
2026-02-09