The Distribution and Regulation of the Cadherin-related Family Member 3 Expression in Human Respiratory Epithelial Cells
Invited conference paper presented and published in conference proceedings

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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 a newly identified human rhinovirus member, human rhinovirus C (RV-C). Intriguingly, the RV-C infection is the leading cause of childhood wheezing illnesses and asthma exacerbation. The rs6967330 in CDHR3 is one of the top SNPs identified in the GWAS, and the SNP effect allele would be an adenine, which eventually turns the amino acid at position 529 to be a tyrosine. A study compared the cellular localization of CDHR3 and RV-C susceptibility between cells transfected with a CDHR3 with a normal cysteine, or a susceptible tyrosine revealed that CDHR3 C529Y had 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. So far, there is not yet a study addressing the distribution and the regulatory mechanism of CDHR3 expression and the downstream mechanism that CDHR3 would contribute to the pathogenesis of wheezing or asthma exacerbation. This study aimed to address these important questions.
Human respiratory tissue paraffin block archives were used to stain for the CDHR3 expression from the upper to the lower airway. Human nasopharyngeal, bronchial and alveolar type II epithelial cells were subjected to the incubation of cytokines (IL4, IL5 and IL13), aeroallergens (Cigarette smoke-conditioned medium(CSM), Lipopolysaccharides (LPS), dust mite extract), dexamethasone and rhinovirus infection. The expression level and its cellular localization of CDHR3 were determined by qPCR and immunofluorescent chemistry. An RV-C infection upon these treatments was performed as a functional test. The RV-C gene expression was measured by qPCR and viral titration using a CDHR3 knock in H1-HeLa cell.
CDHR3 is highly expressed in the epithelia of the nasopharynx and bronchus. However, its expression in the alveolar epithelium is scant in adult but extensive in children. In terms of the effect of cytokine, an incubation of IL-5 would enhance the CDHR3 expression in the respiratory epithelial cells. In the scope of allergens, CSE and LPS would increase the gene expression of CDHR3 in the cells. More importantly, the dexamethasone induced more than six-fold expression of CDHR3 and both CSM and dexamethasone enhanced the replication of rhinovirus.
Study significance
This study provided the information on CDHR3 regulation upon the exposure of airway epithelial cells to relevant stimuli. Hopefully, we can identify the downstream pathways of the CDHR3 that might take part in the airway remodeling in asthma and address part of the pathogenesis of asthma.
All Author(s) ListRenee WY Chan, KP Tao, Joseph GS Tsun, Gary WK Wong, Samuel MW Chow, Judith CW Mak, WM Lee, John M Nicholls, TF Leung
Name of Conference2017 Korean Academy of Allergy Asthma and Clinical Immunology - West Pacific Allergy Symposium - INTERASMA Joint Congress
Start Date of Conference11/05/2017
End Date of Conference13/05/2017
Place of ConferenceSeoul
Country/Region of ConferenceSouth Korea
LanguagesEnglish-United Kingdom

Last updated on 2018-23-05 at 11:46