Center for Molecular Immunology and Infectious Disease, Department of Veterinary and Biomedical Science, The Pennsylvania State University, University Park, PA 16802, USA.
Int Immunol. 2011 Aug;23(8):519-28. doi: 10.1093/intimm/dxr045. Epub 2011 Jun 22.
Multiple pathways converge to result in the overexpression of T(h)17 cells in the absence of either vitamin D or the vitamin D receptor (VDR). CD4(+) T cells from VDR knockout (KO) mice have a more activated phenotype than their wild-type (WT) counterparts and readily develop into T(h)17 cells under a variety of in vitro conditions. Vitamin D-deficient CD4(+) T cells also overproduced IL-17 in vitro and 1,25 dihydroxyvitamin D(3) inhibited the development of T(h)17 cells in CD4(+) T-cell cultures. Conversely, the induction of inducible (i) Tregs was lower in VDR KO CD4(+) T cells than WT and the VDR KO iTregs were refractory to IL-6 inhibition. Host-specific effects of the VDR were evident on in vivo development of naive T cells. Development of naive WT CD4(+) T cells in the VDR KO host resulted in the overexpression of IL-17 and more severe experimental inflammatory bowel disease (IBD). The increased expression of T(h)17 cells in the VDR KO mice was associated with a reduction in tolerogenic CD103(+) dendritic cells. The data collectively demonstrate that T(h)17 and iTreg cells are direct and indirect targets of vitamin D. The increased propensity for development of T(h)17 cells in the VDR KO host results in more severe IBD.
多种途径汇聚导致维生素 D 或维生素 D 受体 (VDR) 缺失时 T(h)17 细胞过度表达。VDR 敲除 (KO) 小鼠的 CD4(+) T 细胞比其野生型 (WT) 细胞具有更活跃的表型，并且在各种体外条件下很容易发展成 T(h)17 细胞。缺乏维生素 D 的 CD4(+) T 细胞也在体外过度产生 IL-17，而 1,25 二羟维生素 D(3) 抑制 CD4(+) T 细胞培养物中 T(h)17 细胞的发育。相反，VDR KO CD4(+) T 细胞中诱导性 (i)Treg 的诱导较低，而 VDR KO iTreg 对 IL-6 抑制无反应。VDR 在宿主特异性方面对幼稚 T 细胞的体内发育有明显影响。VDR KO 宿主中幼稚 WT CD4(+) T 细胞的发育导致 IL-17 的过度表达和更严重的实验性炎症性肠病 (IBD)。VDR KO 小鼠中 T(h)17 细胞的表达增加与耐受型 CD103(+)树突状细胞的减少有关。这些数据共同表明 T(h)17 和 iTreg 细胞是维生素 D 的直接和间接靶标。VDR KO 宿主中 T(h)17 细胞发育的倾向性增加导致更严重的 IBD。
