A vitamin D receptor agonist converts CD4+ T cells to Foxp3+ regulatory T cells in patients with ulcerative colitis

Abstract

One of the pathological features of ulcerative colitis (UC) is the dysfunction of immune regulatory T cells (Treg cells); the pathogenesis is unclear and needs to be further investigated. Vitamin D has immune regulatory functions. This study tests a hypothesis that vitamin D receptor (VDR) regulates Treg cell differentiation. Peripheral blood samples were collected from UC patients and healthy subjects. The correlation between VDR expression and T helper (Th)2 cell differentiation in peripheral CD4⁺ T cells was analyzed. We observed that the expression of VDR was lower, the expression of interleukin (IL)-4 was higher, in peripheral CD4⁺ T cells of UC patients than that in healthy controls. Naive CD4⁺ T cells from VDR deficient mice were prone to differentiating into Th2 cells, which could be adjusted by the presence of VDR agonists. The Th2 polarization status in the peripheral CD4⁺ T cells of UC patients could be converted to regulatory T cells in the culture in the presence of VDR agonists. In conclusion, the peripheral Th2 cells in UC patients can be converted to regulatory T cells by VDR agonists in the culture. The results suggest that administration of VDR agonists at proper dosages may improve the immunity of UC patients.