Cadherin-related family member 3 expression and their regulation in the human respiratory explant cultures
Background: Cadherin-related family member 3 (CDHR3) is identified as a susceptible gene for early childhood asthma with severe exacerbations in genome-wide association study published in 2014. In early 2015, the same transmembrane protein is found to be the cellular receptor for the human rhinovirus C (RV-C). Intriguingly, the HRV-C infection is the leading cause of childhood wheezing illnesses and asthma exacerbation. The rs6967330 in CDHR3 is one of the top SNPs identified and the tyrosine at position 529 is found to be more cell surface expression and yielded ten-fold more RV-C progeny viruses. This finding infers that factors that could induce an overexpression of CDHR3 at the cell surface might lead to a greater susceptibility of RV-C, therefore, a higher chance of wheezing or asthma exacerbation.
Aims: To examine the expression of CDHR3 in human respiratory epithelial cells upon the exposure to wheezing and asthma exacerbation associated risk factors, and its effect in alternating RV-C susceptibility.
Methods: Primary human bronchial and lung explant cultures were derived from bronchial and lung tissues of patients underwent resection in Prince of Wales Hospital. These epithelia were cultured in air-liquid interface cells were pre-incubated with Th2-cytokines, including interleukin(IL)-4, IL-5 and IL-13, aeroallergens including liposaccharides, dust mite extract cigarette smoke extract (CSE) and dexamethasone prior RVs infection. The CDHR3 expression and the RVs replication were monitored at 1, 24, 48 hours post infection. RV-A and RV-B
Results: CDHR3 is highly expressed in the bronchial epithelia but not always in the alveolar epithelial cells. The pre-incubation of IL-5, CSE, liposaccharides and dexamethasone would enhance the CDHR3 expression on these respiratory epithelial cells. More importantly, both CSM and dexamethasone enhanced the replication of rhinovirus.
Conclusions: Cigarette smoke exposure might alter the CDHR3 expression in a way to enhance RV replication. The routine use of dexamethasone in the clinical management of patients with underlying respiratory diseases should be carefully evaluated.
Acknowledgement: CUHK Direct Grants 2015.1.055 to RWYC.