Solitary chemosensory cells are a primary epithelial source of IL-25 in patients with chronic rhinosinusitis with nasal polyps

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 elusiv...

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Bibliographic Details
Published in:Journal of allergy and clinical immunology 2018-08, Vol.142 (2), p.460-469.e7
Main Authors: Kohanski, Michael A., Workman, Alan D., Patel, Neil N., Hung, Li-Yin, Shtraks, Julie P., Chen, Bei, Blasetti, Mariel, Doghramji, Laurel, Kennedy, David W., Adappa, Nithin D., Palmer, James N., Herbert, De'Broski R., Cohen, Noam A.
Format: Article
Language:English
Subjects:
Animals
Asthma
Bone
Breakdowns
Cells, Cultured
Chemoreception
Chemoreceptor Cells - physiology
Chronic Disease
chronic rhinosinusitis with nasal polyps
Cytokines
Doublecortin protein
doublecortin-like kinase 1
Doublecortin-Like Kinases
Enzyme-linked immunosorbent assay
Epithelium
Flow Cytometry
Gnat3 protein
gustducin
Humans
Hypersensitivity
IL-13
IL-25
Immunofluorescence
Immunoglobulins
Inflammation
Interleukin 13
Interleukin-13 - metabolism
Interleukin-17 - metabolism
Intestine
Intracellular Signaling Peptides and Proteins - metabolism
Kinases
Mice
Mucosa
Mucus
Nasal Polyps - immunology
Nose
Otolaryngology
Paranasal Sinuses - pathology
Polyps
Population
Protein Serine-Threonine Kinases - metabolism
Proteins
Respiratory Mucosa - physiology
Respiratory tract
Rhinitis
Rhinitis - immunology
Rhinosinusitis
Sinuses
Sinusitis
Sinusitis - immunology
solitary chemosensory cells
Surgery
Taste - physiology
Transducin - metabolism
type 2 inflammation
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Description
Summary: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. In this study we sought to determine whether the solitary chemosensory cell (SCC) is the predominant source of IL-25 in the sinonasal epithelium. 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. 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. Inflammatory sinus polyps but not adjacent turbinate tissue show expansion of the SCC population, which is the source of epithelial IL-25.
ISSN:0091-6749
1097-6825
DOI:10.1016/j.jaci.2018.03.019