Abstract
BackgroundVitamin 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.ResultsVDR 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.ConclusionsOur 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.
Highlights
Vitamin D receptor (VDR) deficiency contributes to the development of experimental inflammatory bowel disease (IBD) in several different models
Recipients CD8+ T cells from Wild type (WT) and IL-10 KO mice did not induce colitis when transferred to Rag KO recipients and histopathology of the colons from Rag KO mice that received 106 WT or IL-10 KO CD8+ T cells were normal (Figure 1A)
In summary, VDR-deficiency results in the generation of pathogenic CD8+ T cells that contributes to the development of IBD
Summary
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. T cells have been shown to express the VDR, and T cells are both direct and indirect targets of vitamin D. The active form of vitamin D (1,25(OH)2D3) suppressed the development of experimental models of T cell mediated diseases including IBD, multiple sclerosis and type-1 diabetes [6,7]. Vitamin D deficiency and/or VDR deficiency resulted in an exacerbation of experimental IBD [5]. Expression of the VDR does not affect the development of normal numbers of CD4 and CD8αβ T cells in the thymus or in the periphery [5,8,9]. VDR KO CD4+ T cells express more IL-17, and IFN-γ, proliferate more rapidly in a mixed lymphocyte reaction and induce more severe colitis than
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