Oral administration of an active form of vitamin D3 (Calcitriol) decreases atherosclerosis in mice by inducing regulatory t cells and immature dendritic cells with tolerogenic functions

Abstract

Objective- To determine whether the administration of an active form of vitamin D3 (calcitriol) could prevent atherosclerosis through anti-inflammatory actions. Methods and Results- Recent clinical studies have shown that lack of vitamin D3 is a risk factor for cardiovascular events. Oral calcitriol administration decreased atherosclerotic lesions, macrophage accumulation, and CD4 T-cell infiltration at the aortic sinus, when compared with the corresponding observations in control mice. We observed a significant increase in Foxp3+ regulatory T cells and a decrease in CD80+CD86+ dendritic cells (DCs) in the mesenteric lymph nodes, spleen, and atherosclerotic lesions in oral calcitriol-treated mice in association with increased interleukin 10 and decreased interleukin 12 mRNA expression. CD11c+ DCs from the calcitriol group showed reduced proliferative activity of T lymphocytes, suggesting the suppression of DC maturation. Neutralization of CD25 in vivo revealed that calcitriol inhibited atherosclerosis mainly in a regulatory T cell-dependent manner but also partly because of a decrease in DC maturation. Conclusion- Oral calcitriol treatment could prevent the development of atherosclerosis by changing the function or differentiation of DCs and regulatory T cells. These findings suggest that intestinal and systemic immune modulation by calcitriol may be a potentially valuable therapeutic approach against atherosclerosis. © 2010 American Heart Association. All rights reserved.