title: Haploinsufficiency for Stard7 is associated with enhanced allergic responses in lung and skin.
abstract: Allergic asthma is a chronic inflammatory disorder that affects ∼20% of the population worldwide. Microarray analyses of nasal epithelial cells from acute asthmatic patients detected a 50% decrease in expression of Stard7, an intracellular phosphatidylcholine transport protein. To determine whether loss of Stard7 expression promotes allergic responses, mice were generated in which one allele of the Stard7 locus was globally disrupted (Stard7 (+/-) mice). OVA sensitization and challenge of Stard7(+/-) mice resulted in a significant increase in pulmonary inflammation, mucous cell metaplasia, airway hyperresponsiveness, and OVA-specific IgE compared with OVA-sensitized/challenged wild-type (WT) mice. This exacerbation was largely Th2-mediated with a significant increase in CD4(+)IL-13(+) T cells and IL-4, IL-5, and IL-13 cytokines. The loss of Stard7 was also associated with increased lung epithelial permeability and activation of proinflammatory dendritic cells in sensitized and/or challenged Stard7 (+/-) mice. Notably, OVA-pulsed dendritic cells from Stard7(+/-) mice were sufficient to confer an exaggerated allergic response in OVA-challenged WT mice, although airway hyperresponsiveness was greater in Stard7(+/-) recipients compared with WT recipients. Enhanced allergic responses in the lung were accompanied by age-dependent development of spontaneous atopic dermatitis. Overall, these data suggest that Stard7 is an important component of a novel protective pathway in tissues exposed to the extracellular environment.
authors.affiliation: Section of Neonatology, Perinatal and Pulmonary Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH 45229;
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: Division of Immunobiology, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH 45229; and.
authors.forename: Ian
authors.initials: I
authors.lastname: Lewkowich
authors.affiliation: Section of Neonatology, Perinatal and Pulmonary Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH 45229;
authors.forename: Karen
authors.initials: K
authors.lastname: Apsley
authors.affiliation: Section of Neonatology, Perinatal and Pulmonary Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH 45229;
authors.forename: Jill M
authors.initials: JM
authors.lastname: Fritz
authors.affiliation: Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205.
authors.forename: Marsha
authors.initials: M
authors.lastname: Wills-Karp
authors.affiliation: Section of Neonatology, Perinatal and Pulmonary Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH 45229; tim.weaver@cchmc.org.
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Weaver
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D003872:Dermatitis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D017353:Gene Deletion; D057895:Haploinsufficiency; D006967:Hypersensitivity / Q000235:genetics* / Q000276:immunology*; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D010047:Ovalbumin / Q000009:adverse effects / Q000276:immunology; D010539:Permeability; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012867:Skin / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D016207:Cytokines; C000600335:STARD7 protein, mouse; D010047:Ovalbumin