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المؤلفون: Sukhvinder Sidhu, Shaopeng Yuan, S. J. Conway, Erin D. Gordon, M. C. Solon, John V. Fahy, Z.‐E. Wang, Richard M. Locksley, Xiaozhu Huang, Prescott G. Woodruff
المصدر: Clinical and Experimental Allergy
مصطلحات موضوعية: TGF-β, Allergy, Pathophysiology of asthma, Antigens, Fungal, mouse model, Immunology, Inflammation, Original Articles: Editor's Choice: Experimental Models of Allergic Disease, Periostin, Allergic inflammation, 03 medical and health sciences, Mice, 0302 clinical medicine, Transforming Growth Factor beta, medicine, Hypersensitivity, Immunology and Allergy, Animals, Lung, 030304 developmental biology, periostin, 0303 health sciences, business.industry, airway hyperresponsiveness, Aspergillus fumigatus, Matricellular protein, peribronchial fibrosis, respiratory system, asthma, Immunoglobulin E, medicine.disease, 3. Good health, respiratory tract diseases, Mice, Inbred C57BL, Disease Models, Animal, 030228 respiratory system, mucus metaplasia, Respiratory epithelium, Airway Remodeling, IgE, medicine.symptom, Bronchial Hyperreactivity, Airway, business, Cell Adhesion Molecules
الوصف: 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 and Clinical Relevance 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.