title: A protective role for periostin and TGF-β in IgE-mediated allergy and airway hyperresponsiveness.
abstract: BACKGROUND
  The pathophysiology of asthma involves allergic inflammation and remodelling in the airway and airway hyperresponsiveness (AHR) to cholinergic stimuli, but many details of the specific underlying cellular and molecular mechanisms remain unknown. Periostin is a matricellular protein with roles in tissue repair following injury in both the skin and heart. It has recently been shown to be up-regulated in the airway epithelium of asthmatics and to increase active TGF-β. Though one might expect periostin to play a deleterious role in asthma pathogenesis, to date its biological role in the airway is unknown.
  
  
  OBJECTIVE
  To determine the effect of periostin deficiency on airway responses to inhaled allergen.
  
  
  METHODS
  In vivo measures of airway responsiveness, inflammation, and remodelling were made in periostin deficient mice and wild-type controls following repeated intranasal challenge with Aspergillus fumigatus antigen. In vitro studies of the effects of epithelial cell-derived periostin on murine T cells were also performed.
  
  
  RESULTS
  Surprisingly, compared with wild-type controls, periostin deficient mice developed increased AHR and serum IgE levels following allergen challenge without differences in two outcomes of airway remodelling (mucus metaplasia and peribronchial fibrosis). These changes were associated with decreased expression of TGF-β1 and Foxp3 in the lungs of periostin deficient mice. Airway epithelial cell-derived periostin-induced conversion of CD4(+)  CD25(-)  cells into CD25(+) , Foxp3(+)  T cells in vitro in a TGF-β dependent manner.
  
  
  CONCLUSIONS
  Allergen-induced increases in serum IgE and bronchial hyperresponsiveness are exaggerated in periostin deficient mice challenged with inhaled aeroallergen. The mechanism of periostin's effect as a brake on allergen-induced responses may involve augmentation of TGF-β-induced T regulatory cell differentiation.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, CA, USA.
authors.forename: E D
authors.initials: ED
authors.lastname: Gordon
authors.forename: S S
authors.initials: SS
authors.lastname: Sidhu
authors.forename: Z-E
authors.initials: ZE
authors.lastname: Wang
authors.forename: P G
authors.initials: PG
authors.lastname: Woodruff
authors.forename: S
authors.initials: S
authors.lastname: Yuan
authors.forename: M C
authors.initials: MC
authors.lastname: Solon
authors.forename: S J
authors.initials: SJ
authors.lastname: Conway
authors.forename: X
authors.initials: X
authors.lastname: Huang
authors.forename: R M
authors.initials: RM
authors.lastname: Locksley
authors.forename: J V
authors.initials: JV
authors.lastname: Fahy
mesh_terms: D056151:Airway Remodeling; D000818:Animals; D000946:Antigens, Fungal / Q000276:immunology; D001232:Aspergillus fumigatus / Q000276:immunology; D001249:Asthma / Q000276:immunology / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D006967:Hypersensitivity / Q000276:immunology* / Q000503:physiopathology; D007073:Immunoglobulin E / Q000097:blood* / Q000276:immunology; D007249:Inflammation; D008168:Lung / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism*
chemical_list: D000946:Antigens, Fungal; D015815:Cell Adhesion Molecules; C082838:Postn protein, mouse; D016212:Transforming Growth Factor beta; D007073:Immunoglobulin E
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