Role of Nasal Fibroblasts in Airway Remodeling of Chronic Rhinosinusitis: The Modulating Functions Reexamined

Abstract

Chronic rhinosinusitis (CRS) is a multifactorial inflammatory disease of the nose and sinuses that affects more than 10% of the adult population worldwide. Currently, CRS is classified into endotypes according to the inflammatory response (Th1, Th2, and Th17) or the distribution of immune cells in the mucosa (eosinophilic and non-eosinophilic). CRS induces mucosal tissue remodeling. Extracellular matrix (ECM) accumulation, fibrin deposition, edema, immune cell infiltration, and angiogenesis are observed in the stromal region. Conversely, epithelial-to-mesenchymal transition (EMT), goblet cell hyperplasia, and increased epithelial permeability, hyperplasia, and metaplasia are found in the epithelium. Fibroblasts synthesize collagen and ECM, which create a structural skeleton of tissue and play an important role in the wound-healing process. This review discusses recent knowledge regarding the modulation of tissue remodeling by nasal fibroblasts in CRS.

Effect of Air Pollutants on Allergic Inflammation in Structural Cells of the Nasal Mucosa

“…The nasal epithelium is the first line of defense against inhaled allergens, and it releases inflammatory cytokines such as IL-6, IL-25, IL-33, and TSLP, thereby triggering Th2-mediated inflammation [ 15 ]. These cytokines subsequently stimulate nasal fibroblasts, leading to the production of inflammatory mediators and ECM proteins with eosinophil infiltration [ 16 ]. In our experiment on primary nasal epithelial cell (PNEC) and ALI cultures, treatment with PM 2.5 , Zn, and Si solutions increased the expression of epithelial cell-derived cytokines.…”

Thymic Stromal Lymphopoietin and Tezepelumab in Airway Diseases: From Physiological Role to Target Therapy

“…Similar to what happens in bronchial remodeling and high airways, particularly the nasal epithelium, when stimulated by antigens and allergens, produces cytokines such as IL-25, IL-33, and precisely TSLP, which, together with other cytokines such as IL-1, IL-6, and TNF-α, promote the activation of fibroblasts that proliferate and over-accumulate at the basement membrane level. This deposition and production of the cytokines just mentioned promote the secretion of proinflammatory cytokines and chemotactic factors, driving nasal remodeling and polyps generation [ 43 ].…”