Michael A Kohanski1, Alan D Workman1, Neil N Patel1, Li-Yin Hung2, Julie P Shtraks3, Bei Chen4, Mariel Blasetti1, Laurel Doghramji1, David W Kennedy1, Nithin D Adappa1, James N Palmer1, De'Broski R Herbert2, Noam A Cohen5. 1. Department of Otorhinolaryngology-Head and Neck Surgery, Division of Rhinology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pa. 2. Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pa. 3. Department of Otolaryngology-Head and Neck Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, Pa. 4. Department of Otorhinolaryngology-Head and Neck Surgery, Division of Rhinology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pa; Philadelphia Veterans Affairs Medical Center, Philadelphia, Pa. 5. Department of Otorhinolaryngology-Head and Neck Surgery, Division of Rhinology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pa; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pa; Monell Chemical Senses Center, Philadelphia, Pa. Electronic address: Noam.Cohen@uphs.upenn.edu.
Abstract
BACKGROUND: IL-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. OBJECTIVE: In this study we sought to determine whether the solitary chemosensory cell (SCC) is the predominant source of IL-25 in the sinonasal epithelium. METHOD: Flow cytometry and immunofluorescence for SCCs and IL-25 were used to interrogate polyp and turbinate tissue from patients with CRSwNP. Mucus was collected during acute inflammatory exacerbations from patients with CRSwNP or chronic rhinosinusitis without nasal polyps and IL-25 levels determined by using 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. RESULTS: This study demonstrates that a discrete cell type, likely an SCC, characterized by expression of the taste-associated G protein gustducin and the intestinal tuft cell marker doublecortin-like kinase 1, 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 that in vitro IL-13 exposure both increased proliferation and induced apical secretion of IL-25 into the mucosal layer. CONCLUSIONS: Inflammatory sinus polyps but not adjacent turbinate tissue show expansion of the SCC population, which is the source of epithelial IL-25. Published by Elsevier Inc.
BACKGROUND: IL-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. OBJECTIVE: In this study we sought to determine whether the solitary chemosensory cell (SCC) is the predominant source of IL-25 in the sinonasal epithelium. METHOD: Flow cytometry and immunofluorescence for SCCs and IL-25 were used to interrogate polyp and turbinate tissue from patients with CRSwNP. Mucus was collected during acute inflammatory exacerbations from patients with CRSwNP or chronic rhinosinusitis without nasal polyps and IL-25 levels determined by using 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. RESULTS: This study demonstrates that a discrete cell type, likely an SCC, characterized by expression of the taste-associated G protein gustducin and the intestinal tuft cell marker doublecortin-like kinase 1, 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 that in vitro IL-13 exposure both increased proliferation and induced apical secretion of IL-25 into the mucosal layer. CONCLUSIONS: Inflammatory sinus polyps but not adjacent turbinate tissue show expansion of the SCC population, which is the source of epithelial IL-25. Published by Elsevier Inc.
Entities:
Keywords:
IL-13; IL-25; chronic rhinosinusitis with nasal polyps; doublecortin-like kinase 1; gustducin; solitary chemosensory cells; type 2 inflammation
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