Wittke Anja, Chang Andrew, Froicu Monica, Harandi Omid F, Weaver Veronika, August Avery, Paulson Robert F, Cantorna Margherita T
Department of Veterinary and Biomedical Science, The Center for Molecular Immunology and Infectious Disease, The Pennsylvania State University, University Park, PA 16802, USA.
Arch Biochem Biophys. 2007 Apr 15;460(2):306-13. doi: 10.1016/j.abb.2006.12.011. Epub 2007 Jan 2.
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.
缺乏维生素D受体（VDR）的小鼠对气道炎症具有抗性。能够将实验性气道炎症传递给野生型（WT）小鼠的致病性免疫细胞存在于VDR基因敲除（KO）小鼠中并处于预激活状态。此外，VDR KO免疫细胞大量归巢至WT小鼠肺部，足以诱发哮喘症状。相反，将WT脾细胞、Th2细胞和造血细胞转移至VDR KO小鼠时，会诱发一些实验性哮喘症状，但严重程度低于WT对照组。有趣的是，实验性诱导的维生素D缺乏未能反映VDR KO表型，这表明配体缺失和VDR缺乏之间可能存在差异。脂多糖（LPS）在VDR KO小鼠肺部诱导的炎症也低于WT小鼠。这些数据共同表明，维生素D和VDR是肺部炎症的重要调节因子，并且在缺乏VDR的情况下，独立于免疫细胞的肺部环境对环境挑战的反应较弱。
