Vitamin D receptor-deficient mice fail to develop experimental allergic asthma.
The active metabolite of vitamin D (1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3))) is known to modulate the immune response in Th1 cell-directed diseases. To investigate the role of vitamin D in Th2 cell-directed diseases, experimental allergic asthma was induced in vitamin D receptor (VDR) knockout and in wild-type (WT) mice. As expected, WT mice developed symptoms of airway inflammation with an influx of eosinophils, elevated Th2 cytokine levels, mucous production, and airway hyperresponsiveness. The administration of 1,25(OH)(2)D(3) had no effect on asthma severity. The only discernable effect of 1,25(OH)(2)D(3) on experimental allergic asthma in WT mice was an increased expression of two Th2-related genes (soluble CD23 and GATA-3) in lungs of BALB/c mice exposed to Ag through the nasal route only. By contrast, asthma-induced VDR knockout mice failed to develop airway inflammation, eosinophilia, or airway hyperresponsiveness, despite high IgE concentrations and elevated Th2 cytokines. The data suggest that although 1,25(OH)(2)D(3) induced these Th2-type genes, the treatment failed to have any affect on experimental asthma severity. However, VDR-deficient mice failed to develop experimental allergic asthma, suggesting an important role for the vitamin D endocrine system in the generation of Th2-driven inflammation in the lung.
Wittke
Anja
A
Department of Nutrition, Immunology Research Laboratory, Pennsylvania State University, University Park 16802, USA.
Weaver
Veronika
V
Mahon
Brett D
BD
August
Avery
A
Cantorna
Margherita T
MT
D000818:Animals; D001249:Asthma / Q000276:immunology / Q000378:metabolism*; D002117:Calcitriol / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D050990:GATA3 Transcription Factor; D007073:Immunoglobulin E / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D011014:Pneumonia / Q000276:immunology / Q000473:pathology; D018167:Receptors, Calcitriol / Q000172:deficiency* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D017455:Receptors, IgE / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D015534:Trans-Activators / Q000378:metabolism; D015854:Up-Regulation
D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D018167:Receptors, Calcitriol; D017455:Receptors, IgE; D015534:Trans-Activators; D007073:Immunoglobulin E; D002117:Calcitriol