Solitary Chemosensory Cells are a Primary Epithelial Source of Interleukin-25 in Chronic Rhinosinusitis with Nasal Polyps

Publication date: Available online 17 May 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Michael A. Kohanski, Alan D. Workman, Neil N. Patel, Li-Yin Hung, Julie P. Shtraks, Bei Chen, Mariel Blasetti, Laurel Doghramji, David W. Kennedy, Nithin D. Adappa, James N. Palmer, De'Broski R. Herbert, Noam A. Cohen
BackgroundIL-25 can function as an early signal for the respiratory Type 2 response characteristic of allergic asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). In the mouse gut, tuft cells are the epithelial source of IL-25. However, the source of human airway epithelial IL-25 has remained elusive.ObjectiveIn this study, we sought to determine if the solitary chemosensory cell (SCC) is the predominant source of IL-25 in the sinonasal epithelium.MethodFlow cytometry and immunofluorescence for SCCs and IL-25 were used to interrogate polyp and turbinate tissue from patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Mucus was collected during acute inflammatory exacerbations from patients with CRSwNP or CRS without nasal polyps and IL-25 levels determined by Enzyme Linked Immuno-Sorbent Assay (ELISA). Lastly, sinonasal epithelial cultures derived from polyp and turbinate tissue were stimulated with IL-13 and analyzed for SCC proliferation and IL-25 production.ResultsThis study demonstrates that a discrete cell type, likely a solitary chemosensory cell (SCC), characterized by expression of the taste-associated G-protein, gustducin, and the intestinal tuft cell marker, doublecortin-like kinase 1, DCAMKL1, is the predominant source of IL-25 in the human upper airway. Additionally, we show that patients with CRSwNP have increased numbers of SCCs in nasal polyp tissue and in-vitro IL-13 exposure both increased proliferation and induced apical secretion of IL-25 into the mucus layer.ConclusionsInflammatory sinus polyps but not adjacent turbinate tissue have an expansion of a solitary chemosensory cell population that is the source of epithelial IL-25.

Teaser

Solitary chemosensory cells are the epithelial source of IL-25 in nasal polyps and may be a marker of upper airway inflammations.


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