Airway Epithelial KIF3A Regulates Th2 Responses to Aeroallergens
| Autor: | Mark B. Ericksen, Premkumar Vummidi Giridhar, Anusha Sridharan, Gurjit K. Khurana Hershey, Priya Rajavelu, Joseph A. Kitzmiller, Sheila M. Bell, Anjaparavanda P. Naren, Jeffrey A. Whitsett, Eric B. Brandt, Cheng-Lun Na, Matthew Kofron, Changsuk Moon |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Chemokine Mucociliary clearance Immunology Kinesins Mice Transgenic Inflammation Respiratory Mucosa Article Pathogenesis Mice 03 medical and health sciences Th2 Cells medicine Animals Immunology and Allergy Pulmonary pathology Lung CCL11 Goblet cell biology Aspergillus fumigatus Epithelial Cells Allergens respiratory system medicine.disease Asthma respiratory tract diseases 030104 developmental biology medicine.anatomical_structure Motile cilium biology.protein Cytokines medicine.symptom |
| Zdroj: | The Journal of Immunology. 197:4228-4239 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1600926 |
| Popis: | KIF3A, the gene encoding kinesin family member 3A, is a susceptibility gene locus associated with asthma; however, mechanisms by which KIF3A might influence the pathogenesis of the disorder are unknown. In this study, we deleted the mouse Kif3a gene in airway epithelial cells. Both homozygous and heterozygous Kif3a gene–deleted mice were highly susceptible to aeroallergens from Aspergillus fumigatus and the house dust mite, resulting in an asthma-like pathology characterized by increased goblet cell metaplasia, airway hyperresponsiveness, and Th2-mediated inflammation. Deletion of the Kif3a gene increased the severity of pulmonary eosinophilic inflammation and expression of cytokines (Il-4, Il-13, and Il-17a) and chemokine (Ccl11) RNAs following pulmonary exposure to Aspergillus extract. Inhibition of Kif3a disrupted the structure of motile cilia and impaired mucociliary clearance, barrier function, and epithelial repair, demonstrating additional mechanisms by which deficiency of KIF3A in respiratory epithelial cells contributes to pulmonary pathology. Airway epithelial KIF3A suppresses Th2 pulmonary inflammation and airway hyperresponsiveness following aeroallergen exposure, implicating epithelial microtubular functions in the pathogenesis of Th2-mediated lung pathology. |
| Databáze: | OpenAIRE |
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