IL-4Rα expression by airway epithelium and smooth muscle accounts for nearly all airway hyperresponsiveness in murine allergic airway disease
| Autor: | Fred D. Finkelman, Christopher G. McKnight, Crystal Potter |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Immunology Receptors Cell Surface Respiratory Mucosa Biology Article Mice 03 medical and health sciences 0302 clinical medicine Metaplasia Hypersensitivity Respiratory Hypersensitivity medicine Animals Humans Immunology and Allergy Eosinophilia Antigens Dermatophagoides Receptor Cells Cultured Mice Knockout House dust mite Mice Inbred BALB C Goblet cell Interleukin-13 Pyroglyphidae Muscle Smooth respiratory system biology.organism_classification Epithelium respiratory tract diseases Disease Models Animal 030104 developmental biology medicine.anatomical_structure Respiratory epithelium Female Goblet Cells Interleukin-4 medicine.symptom Signal transduction Signal Transduction 030215 immunology |
| Zdroj: | Mucosal immunology |
| ISSN: | 1933-0219 |
| DOI: | 10.1038/s41385-019-0232-7 |
| Popis: | Airway hyperresponsiveness (AHR) often defines asthma. Murine allergic airway disease (AAD), like human eosinophilic asthma, is characterized by AHR, eosinophilia, goblet cell metaplasia (GCM), smooth muscle hypercontractility and increased production of IL-4 and IL-13—cytokines that induce these characteristics by binding to the IL-4Rα chain. We evaluated the epithelial and smooth muscle IL-4Rα-dependent contributions to AHR of BALB/c mice that possessed 0–2 functional IL-4Rα alleles and had airway disease induced by house dust mite extract (HDM) or exogenous IL-13. Two functional IL-4Rα alleles were required for maximal AHR, while only one functional allele was required for maximal GCM and systemic IL-4/IL-13 levels. Deletion of IL-4Rα from both smooth muscle and epithelial cells inhibited AHR >83% in mice with two functional IL-4Rα alleles. In mice with one functional IL-4Rα allele, selective epithelial cell IL-4Rα deletion maximally inhibited AHR, while selective smooth muscle IL-4Rα deletion decreased IL-13-induced, but not HDM-induced, AHR. Less IL-4Rα signaling is required to maximize the epithelial cell contribution to AHR compared to the smooth muscle contribution to AHR. Additionally, epithelial cell responses to IL-4/IL-13 can increase the IL-4Rα-dependent smooth muscle contribution to AHR. These findings carry increasing relevance as IL-4Rα-targeted therapy is administered to human asthmatics. |
| Databáze: | OpenAIRE |
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