Regulatory T cells in atherosclerosis and strategies to induce the endogenous atheroprotective immune response.

Atherosclerosis is a chronic inflammatory disease, in which multiple types of immune cells are involved. Th1 and Th17 cells play a prominent role in induction and progression of local inflammation in the atherosclerotic plaque. Regulatory T cells (Tregs) can be also found in the plaque but their numbers are decreased and function may be impaired. Tregs are the master modulators of the immune system possessing the immunosuppressive capacity to prevent unfavorable immune responses and maintain tolerance to self-antigens. These cells play the atheroprotective role by inhibiting Th1/Th17-mediated proinflammatory response and down-regulating the antigen-presenting function of dendritic cells (DCs). Tregs mediate the immune response through the cell-to-cell contacts and secretion of anti-inflammatory cytokines IL-10 and TNF-beta. In addition to the natural CD4(+)CD25(+)Foxp3(+) Tregs presented in the thymus, there are several subtypes of inducible Tregs that can be induced from naïve CD4(+) T cells by tolerogenic DCs in the periphery. Thus, stimulation of the immunosuppressive activity of Tregs and increasing numbers of Tregs and immunocompetent DCs has a great clinical potential in prevention and treatment of atherosclerosis and its vascular complications. A promising strategy to induce the anti-atherogenic immune response is an oral administration of anti-inflammatory immunomodulators capable to activate the intestine immune tolerance by recruiting mucosal tolerogenic DCs and inducing Tregs. Induced Tregs can then migrate to the inflamed vascular sites and reduce atherogenesis.