Immune Cell Responses and Mucosal Barrier Disruptions in Chronic Rhinosinusitis

Abstract

Chronic rhinosinusitis (CRS) is one of the most common presentations of upper airway illness and severely affects patient quality of life. Its frequency is not surprising given levels of environmental exposure to microbes, pollutants, and allergens. Inflammatory cells, inflammatory cytokine and chemokine production, and airway remodeling have been detected in the sinonasal mucosae of CRS patients, although the precise pathophysiological mechanisms causing such persistent inflammation remain unclear. Given its high prevalence and considerable associated morbidity, continued research into CRS is necessary to increase our understanding of factors likely to contribute to its pathogenesis, and facilitate the development of novel therapeutic strategies to improve treatment. The purpose of this review is to summarize the current state of knowledge regarding immune cell responses and epithelial alterations in CRS.

Keywords: Chronic rhinosinusitis; Cytokines; Eosinophils; Epithelial-mesenchymal transition; Nasal mucosa; Nasal polyps.

Figure 1. Altered epithelial barrier function contributes to type 2-mediated inflammation in chronic rhinosinusitis and nasal polyps. Several factors, including allergens, bacteria, viruses, and fungi can activate nasal epithelial cells to produce innate cytokines that activate type 2 innate lymphoid cells. IL-5 derived from these latter contributes to airway eosinophilia, whereas IL-13 acts directly on the epithelium to drive goblet cell metaplasia. IL-4 promotes IgE production by B cells, which causes mast cell and basophil activation. Mast cells activate fibroblasts to produce collagen fibers. In addition, mast cells produce mediators that can induce vasodilation and tissue edema. Nasal epithelial cells can also undergo epithelial-to-mesenchymal transition under hypoxia, as observed in chronic rhinosinusitis and nasal polyps. EMT, epithelial-to-mesenchymal transition; ILC2, type 2 innate lymphoid cell.