Dendritic Cells in Atherogenesis: Possible Novel Targets for Prevention of Atherosclerosis

Abstract

Atherosclerosis has been recognized as an inflammatory disease of the arterial wall, involving innate and adaptive immunity. Effector T cells are differentiated from naïve T cells stimulated by antigen-presenting cells such as macrophages and dendritic cells (DCs) and play critical roles in atherogenesis. Accumulating evidence revealed that several subsets of regulatory T cells (Tregs) inhibit atherosclerotic lesion formation via inhibiting the inflammatory response of effector T cells. In addition, the contribution of DCs to atherogenesis has been demonstrated. DCs have different functions for either stimulating or inhibiting T cell function depending on their origin and maturation stage. In particular, immature DCs, which have potential for inducing Tregs and inhibiting effector T cells, are sometimes called ‘tolerogenic DCs’ and suppress immune responses. Epidemiological studies have highlighted the increasing prevalence of vitamin D₃ deficiency and its association with increased risks of cardiovascular diseases. Some studies have raised interest in the immunomodulatory properties of vitamin D₃ beyond its well-established role in bone and calcium metabolism. The active form of vitamin D₃ (calcitriol) induces Tregs and tolerogenic DCs, which are both involved in maintaining immunologic tolerance to self and harmless antigens. Interestingly, recent evidence suggested that DCs in the intestinal immune system are involved in inducing Tregs; modulating the function of DCs and Tregs in the intestinal immune system might have beneficial effects on atherosclerosis. In this review, we focus on the function of DCs in vascular diseases and discuss vitamin D₃ therapy for the prevention of atherosclerosis.