Contribution of Epithelial Cell Dysfunction to the Pathogenesis of Chronic Rhinosinusitis with Nasal Polyps

Abstract

Background In the past, the airway epithelium was thought to be primarily an inert physical barrier. We now know that the upper airway epithelium plays a critical role in both innate and adaptive immunity, and that epithelial dysfunction is strongly associated with inflammatory airway disease. The pathogenesis of chronic rhinosinusitis is poorly understood, but growing evidence supports a key role for the airway epithelium in the pathophysiology of the disease. Objective The purpose of this study is to explore our current understanding of how dysfunction in human sinonasal epithelial cells (HSNECs) contributes to the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) and to examine how current and developing therapies affect epithelial cell functions. Methods A literature review of papers published in English pertaining to epithelial cell dysfunction in patients with CRSwNP was performed using the PubMed database. The search utilized combinations of the following key words: sinusitis, polyps, epithelium, pathophysiology, barrier function, dendritic cells, eosinophils, T cells, complement, mucociliary clearance, vitamin D, cytokines, chemokines, taste receptors, steroids, saline, and therapy. Results HSNEC mucociliary clearance, barrier function, secretion of cytokines, influence on dendritic cells, influence on T-cells, regulation of eosinophils, vitamin D metabolism, complement production, and taste receptor function are altered in patients with CRSwNP and contribute to the pathogenesis of the disease. Current therapies utilized to manage CRSwNP counteract the effects of HSNEC dysfunction and relieve key symptoms of the disease. Conclusion HSNECs are key players in both innate and adaptive immunity, and altered epithelial functions are closely intertwined with the pathogenesis of CRSwNP. Our review supports further investigation of altered HSNEC function in patients with CRSwNP and supports development of novel epithelial-targeted therapies for its management.

Pathogenesis of chronic rhinosinusitis with nasal polyps: role of IL-6 in airway epithelial cell dysfunction

“…We developed air-liquid interface (ALI) cultures of primary differentiated human nasal epithelial cells (HNEC) that can be used as an in vitro wound repair and ciliary beating evaluation model. Our results suggest new mechanisms of epithelial cell-IL relationships and may lead to the identification of novel therapeutic pathways that could improve treatment for patients with CRSwNP [8].…”

“…In conclusion, IL-6 trans-signaling could induce chronic proliferation of epithelial cells after wound healing of the epithelial barrier and growth of NPs. Finally, mucociliary dysfunction could be a prominent pathophysiological feature of CRSwNP [8,55,56]; however, the precise mechanisms underlying mucociliary dysfunction are still unclear. A previous study demonstrated in the same in vitro primary model of cultures that IFN-γ and IL-13 both significantly reduced ciliated cell differentiation and CBF in CRSwNP patients [57].…”

“…Mucociliary clearance is one of the major lines of defense of the respiratory system. Overall, the epithelial barrier dysfunction could be involved in physiopathology of nasal polyps [8,10,60]. Further studies are needed to evaluate the IL-6 effect on mucosal barrier (especially on expression of tight junctions and monolayer permeability).…”

“…Respiratory epithelium in NPs exhibits morphological changes consistent with epithelial dysfunction, including basal cell proliferation, goblet cell hyperplasia and the loss of differentiation of ciliated cells [3][4][5][6][7]. A recent review [8] describes how dysfunction of the airway epithelium contributes to the pathogenesis of CRSwNP and suggests that mucociliary clearance [9] and maintenance barrier function [10] could be altered in NP epithelial cells. Furthermore, dysregulation of epithelial wound repair with an inability to obtain ad integrum repair of the nasal airway epithelium has been described in NPs [3,11,12].…”

Something for Everyone in Rhinology and Allergy

“…A different aspect of nasal polyp pathogenesis is the subject of a review by Wynne et al, who report on the role of epithelial cell dysfunction in this disease process. 2 They identify alterations in numerous cellular processes, including mucociliary clearance, vitamin D metabolism and influence on other immunologic cells. Further understanding of these and other factors relevant to CRS may suggest possible therapeutic targets.…”