Epithelial cell function and remodeling in nasal polyposis

Abstract

Objective: To review the latest discoveries on airway epithelial cell diversity and remodeling in type 2 inflammation, including nasal polyposis.

Data sources: Reviews and primary research manuscripts were identified from PubMed, Google, and Bioarchives, using the search words airway epithelium, nasal polyposis, or chronic rhinosinusitis with nasal polyposis AND basal cell, ciliated cell, secretory cell, goblet cell, neuroendocrine cell, pulmonary neuroendocrine cell, ionocyte, brush cell, solitary chemosensory cell, microvillus cell, or tuft cell.

Study selections: Studies were selected based on novelty and likely relevance to airway epithelial innate immune functions or the pathobiology of type 2 inflammation.

Results: Airway epithelial cells are more diverse than previously appreciated, with specialized subsets, including ionocytes, solitary chemosensory cells, and neuroendocrine cells that contribute to important innate immune functions. In chronic rhinosinusitis with nasal polyposis, the composition of the epithelium is significantly altered. Loss of ciliated cells and submucosal glands and an increase in basal airway epithelial progenitors leads to loss of innate immune functions and an expansion of proinflammatory potential. Type 2 cytokines play a major role in driving this process.

Conclusion: Airway epithelial remodeling in chronic rhinosinusitis is extensive, leading to loss of innate immune function and enhanced proinflammatory potential. The mechanisms driving airway remodeling and its sequelae deserve further attention before restitution of epithelial differentiation can be considered a reasonable therapeutic target.

Figure 1.

Type 2 immunopathology in chronic rhinosinusitis with nasal polyposis. Innate T2 inflammation (left) can be elicited by the activation of tissue-resident ILC2s (I) and mast cells (MCs) by TSLP, IL-25, and IL-33. Mast cells and ILCs make IL-13. Mast cells can additionally make eicosanoids such as prostaglandin D2. Adaptive T2 inflammation (right) involves the conventional DC-mediated generation of Th2 cells (T) and the subsequent production of IgE by B cells (B). This also leads to MC production of IL-13 and eicosanoids. Each pathway leads to tissue eosinophilia (Eo). DC, dendritic cell; IgE, immunoglobulin E; IL, interleukin; TSLP, thymic stromal lymphopoietin.

Figure 2.

Workforce diversity provides a coordinated innate immune defense in the airway epithelium. Airway EpCs include ciliated cells (tan), goblet cells (pink/light pink), basal progenitor cells (burgundy), ionocytes (green), neuroendocrine cells (violet), and SCCs (blue). On the lumenal side, effective mucociliary clearance requires mucin generation (goblet cells), water/solute regulation (ionocytes), and ciliary beat (ciliated cells). Epithelial cells prevent microbial replication through the generation of iron-binding molecules such as lactoferrin (secretory cells). Several EpCs secrete small amphipathic antimicrobial peptides with microbiocidal activity and high-molecular-weight glycoproteins that trap microbes and function as chemoattractants. On the basal side, DCs are mobilized to initiate adaptive immunity, which is patterned by CysLTs (SCC product) and TSLP (basal cell product). Mast cells (MCs) produce eicosanoids in response to IL-33 and TSLP (basal cell products). Type 2 innate lymphoid cells (ILC2) make IL-5 in response to CGRP (NEC product); IL-5 and IL-13 in response to basal cell products IL-33 and TSLP and the SCC product IL-25; and IL-4, IL-5, and IL-13 in response to IL-33 (basal cell product) and CysLTs (SCC product). Eosinophils (Eo) are recruited to tissue by eotaxins including CCL11, CCL24, and CCL26 produced in many secretory cells. Dorsal root ganglion (DRG) nerves are activated by acetyl choline (SCC product) and by CGRP and GABA (NEC products). CGRP, calcitonin gene-related peptide; CysLT, cysteinyl leukotriene; DC, dendritic cell; EpC, epithelial cell; GABA, g-aminobutyric acid; IL, interleukin; NEC, neuroendocrine cell; SCC, solitary chemosensory cell; TSLP, thymic stromal lymphopoietin.