Vitamin D receptor expression by the lung micro-environment is required for maximal induction of lung inflammation.
Mice lacking the vitamin D receptor (VDR) are resistant to airway inflammation. Pathogenic immune cells capable of transferring experimental airway inflammation to wildtype (WT) mice are present and primed in the VDR KO mice. Furthermore, the VDR KO immune cells homed to the WT lung in sufficient numbers to induce symptoms of asthma. Conversely, WT splenocytes, Th2 cells and hematopoetic cells induced some symptoms of experimental asthma when transferred to VDR KO mice, but the severity was less than that seen in the WT controls. Interestingly, experimentally induced vitamin D deficiency failed to mirror the VDR KO phenotype suggesting there might be a difference between absence of the ligand and VDR deficiency. Lipopolysaccharide (LPS) induced inflammation in the lungs of VDR KO mice was also less than in WT mice. Together the data suggest that vitamin D and the VDR are important regulators of inflammation in the lung and that in the absence of the VDR the lung environment, independent of immune cells, is less responsive to environmental challenges.
Wittke
Anja
A
Department of Veterinary and Biomedical Science, The Center for Molecular Immunology and Infectious Disease, The Pennsylvania State University, University Park, PA 16802, USA.
Chang
Andrew
A
Froicu
Monica
M
Harandi
Omid F
OF
Weaver
Veronika
V
August
Avery
A
Paulson
Robert F
RF
Cantorna
Margherita T
MT
D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006412:Hematopoietic Stem Cells / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007113:Immunity, Innate; D008024:Ligands; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D018345:Mice, Knockout; D018167:Receptors, Calcitriol / Q000235:genetics / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D014807:Vitamin D / Q000276:immunology*
D008024:Ligands; D008070:Lipopolysaccharides; D018167:Receptors, Calcitriol; D014807:Vitamin D