Vitamin D receptor expression controls proliferation of naïve CD8+ T cells and development of CD8 mediated gastrointestinal inflammation.

Abstract

BACKGROUND:

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.

RESULTS:

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.

CONCLUSIONS:

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.

• Authors: Jing Chen, Danny Bruce, Margherita T Cantorna
• Journal: BMC immunology (BMC Immunol) Vol. 15 Pg. 6 (Feb 07 2014) ISSN: 1471-2172 [Electronic] England
• PMID: 24502291 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Interleukin-2
• Receptors, Calcitriol
• Leukocyte Common Antigens

Topics

• Adoptive Transfer
• Animals
• CD4-Positive T-Lymphocytes (immunology, metabolism)
• CD8-Positive T-Lymphocytes (drug effects, immunology, metabolism)
• Colitis (genetics, immunology, metabolism)
• Disease Models, Animal
• Gene Expression Regulation
• Inflammatory Bowel Diseases (genetics, immunology, metabolism)
• Interleukin-2 (pharmacology)
• Leukocyte Common Antigens (metabolism)
• Lymphocyte Activation (drug effects, immunology)
• Mice
• Mice, Knockout
• Receptors, Calcitriol (genetics, metabolism)