title: Airway Epithelial KIF3A Regulates Th2 Responses to Aeroallergens.
abstract: 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.
authors: Division of Neonatology, Perinatal and Pulmonary Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229.
authors: Premkumar Vummidi
authors: 0000-0001-9029-7407
authors: PV
authors: Giridhar
authors: Division of Neonatology, Perinatal and Pulmonary Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229.
authors: Sheila M
authors: SM
authors: Bell
authors: Division of Neonatology, Perinatal and Pulmonary Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229.
authors: Anusha
authors: A
authors: Sridharan
authors: Division of Neonatology, Perinatal and Pulmonary Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229.
authors: Priya
authors: P
authors: Rajavelu
authors: Division of Neonatology, Perinatal and Pulmonary Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229.
authors: Joseph A
authors: JA
authors: Kitzmiller
authors: Division of Neonatology, Perinatal and Pulmonary Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229.
authors: Cheng-Lun
authors: 0000-0003-2771-8306
authors: CL
authors: Na
authors: Division of Developmental Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229.
authors: Matthew
authors: M
authors: Kofron
authors: Division of Asthma Research, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229; and.
authors: Eric B
authors: 0000-0003-0617-4100
authors: EB
authors: Brandt
authors: Division of Asthma Research, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229; and.
authors: Mark
authors: M
authors: Ericksen
authors: Division of Pulmonary Medicine, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229.
authors: Anjaparavanda P
authors: 0000-0003-2834-051X
authors: AP
authors: Naren
authors: Division of Pulmonary Medicine, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229.
authors: Changsuk
authors: C
authors: Moon
authors: Division of Asthma Research, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229; and.
authors: Gurjit K
authors: 0000-0001-6663-977X
authors: GK
authors: Khurana Hershey
authors: Division of Neonatology, Perinatal and Pulmonary Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229; jeff.whitsett@cchmc.org.
authors: Jeffrey A
authors: JA
authors: Whitsett
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D001232:Aspergillus fumigatus / Q000276:immunology*; D001249:Asthma / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology* / Q000473:pathology; D016547:Kinesins / Q000235:genetics / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D020545:Respiratory Mucosa / Q000276:immunology* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology
chemical_list: D000485:Allergens; D016207:Cytokines; C490202:Kif3a protein, mouse; D016547:Kinesins