Abstract
Rhinovirus (RV) infection of the bronchial epithelium (BE) is the main trigger of severe asthma exacerbations. Interestingly, severe asthmatic also exhibit an increase of bronchial smooth muscle (BSM) mass. A decreased distance between BE and BSM is correlated to the severity of the disease and suggest a role of BSM cells migration toward epithelium in BSM remodelling of severe asthmatic patients.
We investigate chemotaxis effect of RV-infected BE on BSM cells using primary BE and BSM cells obtained from non-asthmatic and severe asthmatic patients. BSM migration was assessed by live video microscopy in response to RV-infected BE supernatant. Our study unveiled the implication of CXCL10/CXCR3 axis which has been analysed using ELISA, immunostaining, western blot, flow cytometry and real-time calcium fluorescence.
We demonstrate a specific migration of severe asthmatic BSM cells towards RV-infected BE. Transcriptomic analysis show an increase of CXCL-10 in RV-infected supernatant which was confirmed both in vitro and ex vivo. On the BSM side, the blocking of CXCL10 receptor (i.e CXCR3), abolished severe asthmatic BSM cells migration. CXCR3-A and B isoforms have antagonist effects on cell migration (activation and inhibition respectively). We found an increased expression and activation of CXCR3-B pathway in non-asthmatic BSM cells in response to CXCL10. However, CXCR3-A expression and calcium dependant activation are increased in severe asthmatic BSM cells.
This CXCR3 isoform-dependant mechanism unveils a new role of rhinovirus-infection on BSM remodelling which could be a new therapeutic target against this unmet need in severe asthma.
Footnotes
Cite this article as: European Respiratory Journal 2021; 58: Suppl. 65, PA2316.
This abstract was presented at the 2021 ERS International Congress, in session “Prediction of exacerbations in patients with COPD”.
This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
- Copyright ©the authors 2021