Rhinovirus induces airway remodeling: what are the physiological consequences?

Respiratory Research

Review

Cynthia J. Koziol-White¹  Cassandra Spector¹  Reynold A. Panettieri¹  Camden M. De Sanctis¹ 

[1] Rutgers Institute for Translation Medicine and Science, New Brunswick, NJ, USA;

关键词: Airway remodeling;    Rhinovirus;    Asthma;    Airway epithelium;    Airway smooth muscle;    Fibroblasts;    Myofibroblasts;    Airway hyperresponsiveness;   

DOI  :  10.1186/s12931-023-02529-9

 received in 2023-08-11, accepted in 2023-09-01,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundRhinovirus infections commonly evoke asthma exacerbations in children and adults. Recurrent asthma exacerbations are associated with injury-repair responses in the airways that collectively contribute to airway remodeling. The physiological consequences of airway remodeling can manifest as irreversible airway obstruction and diminished responsiveness to bronchodilators. Structural cells of the airway, including epithelial cells, smooth muscle, fibroblasts, myofibroblasts, and adjacent lung vascular endothelial cells represent an understudied and emerging source of cellular and extracellular soluble mediators and matrix components that contribute to airway remodeling in a rhinovirus-evoked inflammatory environment.Main bodyWhile mechanistic pathways associated with rhinovirus-induced airway remodeling are still not fully characterized, infected airway epithelial cells robustly produce type 2 cytokines and chemokines, as well as pro-angiogenic and fibroblast activating factors that act in a paracrine manner on neighboring airway cells to stimulate remodeling responses. Morphological transformation of structural cells in response to rhinovirus promotes remodeling phenotypes including induction of mucus hypersecretion, epithelial-to-mesenchymal transition, and fibroblast-to-myofibroblast transdifferentiation. Rhinovirus exposure elicits airway hyperresponsiveness contributing to irreversible airway obstruction. This obstruction can occur as a consequence of sub-epithelial thickening mediated by smooth muscle migration and myofibroblast activity, or through independent mechanisms mediated by modulation of the β2 agonist receptor activation and its responsiveness to bronchodilators. Differential cellular responses emerge in response to rhinovirus infection that predispose asthmatic individuals to persistent signatures of airway remodeling, including exaggerated type 2 inflammation, enhanced extracellular matrix deposition, and robust production of pro-angiogenic mediators.ConclusionsFew therapies address symptoms of rhinovirus-induced airway remodeling, though understanding the contribution of structural cells to these processes may elucidate future translational targets to alleviate symptoms of rhinovirus-induced exacerbations.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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