Chen Jing, Bruce Danny, Cantorna Margherita T
Department of Veterinary and Biomedical Science, The Pennsylvania State University, University Park, PA 16802, USA.
BMC Immunol. 2014 Feb 7;15:6. doi: 10.1186/1471-2172-15-6.
Vitamin D receptor (VDR) deficiency contributes to the development of experimental inflammatory bowel disease (IBD) in several different models. T cells have been shown to express the VDR, and T cells are targets of vitamin D. In this article we determined the effects of VDR expression on CD8+ T cells.
VDR KO CD8+ T cells, but not WT CD8+ T cells, induced colitis in Rag KO recipients. In addition, co-transfer of VDR KO CD8+ T cells with naïve CD4+ T cells accelerated colitis development. The more severe colitis was associated with rapidly proliferating naïve VDR KO CD8+ T cells and increased IFN-γ and IL-17 in the gut. VDR KO CD8+ T cells proliferated in vitro without antigen stimulation and did not downregulate CD62L and upregulate CD44 markers following proliferation that normally occurred in WT CD8+ T cells. The increased proliferation of VDR KO CD8+ cells was due in part to the higher production and response of the VDR KO cells to IL-2.
Our data indicate that expression of the VDR is required to prevent replication of quiescent CD8+ T cells. The inability to signal through the VDR resulted in the generation of pathogenic CD8+ T cells from rapidly proliferating cells that contributed to the development of IBD.
在多种不同模型中，维生素D受体（VDR）缺乏会促使实验性炎症性肠病（IBD）的发展。已表明T细胞表达VDR，且T细胞是维生素D的作用靶点。在本文中，我们确定了VDR表达对CD8⁺T细胞的影响。
VDR基因敲除（KO）的CD8⁺T细胞而非野生型（WT）CD8⁺T细胞，可在Rag基因敲除受体中诱发结肠炎。此外，将VDR基因敲除的CD8⁺T细胞与幼稚CD4⁺T细胞共同转移可加速结肠炎的发展。更严重的结肠炎与幼稚VDR基因敲除的CD8⁺T细胞快速增殖以及肠道中干扰素-γ（IFN-γ）和白细胞介素-17（IL-17）增加有关。VDR基因敲除的CD8⁺T细胞在无抗原刺激的情况下可在体外增殖，且在增殖后不会像野生型CD8⁺T细胞那样下调CD62L并上调CD44标志物。VDR基因敲除的CD8⁺细胞增殖增加部分归因于VDR基因敲除细胞对白细胞介素-2（IL-2）的更高产生和反应。
我们的数据表明，需要VDR的表达来防止静止CD8⁺T细胞的复制。无法通过VDR发出信号导致从快速增殖的细胞中产生致病性CD8⁺T细胞，这促进了IBD的发展。
