Altered CDHR3 Expression in asthmatic children bronchial epithelium - 09/05/26

Asthma represents the most frequent chronic inflammatory condition among children. Infections of the bronchial epithelium (BE) by viruses are the primary cause of exacerbations with rhinoviruses (RV) detected in 85% of cases, especially RV-C, responsible for 67.5% of paediatric cases. The RV-C uses cadherin-related family member 3 (CDHR3) as a unique receptor, enabling its entry and then an efficient replication. CDHR3 variants, notably the rs6967330 A allele increases CDHR3 expression, increasing RV-C infection in nasal airway epithelial cells from childhood asthma cohort [1 JACI 2019; 144:962-971.

Haga clic aquí para ir a la sección de Referencias] . They also showed that CDHR3 knockout reduces transepithelial resistance, suggesting that its expression influences epithelial barrier integrity. This variant is linked to higher asthma exacerbation rates and greater RV-C infection risk in children hospitalized for respiratory infections [2 Virol. J 22;29.

Haga clic aquí para ir a la sección de Referencias] . We hypothesize that CDHR3 is overexpressed in asthmatic vs non-asthmatic paediatric BE, promoting viral entry and replication, weakening more the barrier, and aggravate asthma exacerbations.

Cell culture: BE cells from bronchial brushing of children were seeded (100,000 cells) on ALI transwells (0.4 μm pores, Corning Costar) with ALI medium (StemCell) at the basal pole.

RV infection: BE were infected with RV-C at MOI 0.1. After 1 h, the mix was removed, and experiments performed 24 h later.

Immunofluorescence: BE cells were fixed (4% PFA), permeabilized (Triton X-100), blocked (4% BSA), and incubated overnight at 4 °C with primary antibodies (1: 500), followed by Alexa Fluor™ 488/568 secondary antibodies. Membranes were excised, mounted (Fluoromount™), and imaged using an SPE1 confocal microscope. Image analysis was done with ImageJ and Imaris.

Western blotting: total proteins from bronchial epithelial cells were extracted, quantified, and analyzed by Western blot to detect CDHR3, ZO-1, and Claudin-1, with normalization to total protein levels.

TEER: TEER was measured using a specialized voltmeter (Evom ³ , World Precision Instruments) in bronchial epithelial cells from non-asthmatic and asthmatic patients at baseline and every 24 h for 5 days following RV-C infection.

Under basal conditions, BE composition did not differ between healthy and asthmatic children. However, paediatric asthmatic BE showed increased CDHR3 expression. Moreover, BE impermeability was reduced. The increased CDHR3 expression could promote higher susceptibility to viral infection, which, may further exacerbate the impairment of epithelial barrier function observed in infected asthmatic BE.

Higher CDHR3 expression in asthmatic BE may compromise barrier integrity by facilitating RV-C infection and worsening asthma exacerbations.