Dendritic cells and their role in atherogenesis

Abstract

Dendritic cells (DCs) are the most potent professional antigen-presenting cells with the unique ability of primary immune response initiation. DCs originate from bone marrow progenitors, which circulate in the peripheral blood and subsequently penetrate peripheral tissues, where they give rise to immature DCs. In peripheral tissues, DCs continuously monitor the microenvironment and, when the cells encounter 'danger' signals, DCs undergo differentiation and maturation. Maturing DCs usually migrate to lymphatic tissues, where they form contacts with T cells to initiate a primary immune response. DCs were identified in arteries in 1995 and since then, further knowledge has been gained about the peculiarities of vascular-associated DCs and their role in atherosclerosis. Immune reactions toward modified lipoproteins and other factors ignited by resident vascular DCs as well as by newly arrived DCs, which originate from blood monocytes, are believed to destabilize arterial homeostasis from very earlier stages of atherogenesis. There is a remarkable heterogeneity of DCs in atherosclerotic lesions. Some DCs mature and become capable of forming clusters with T cells directly within the arterial wall. The predictive value of the numbers of circulating DC precursors in coronary artery disease and in atherosclerosis has been assessed, and it has been shown that DCs have a role in plaque destabilization. Over recent decades, DCs have proven to be a valuable instrument in immunotherapy approaches against cancer and various autoimmune diseases, and this explains the demand that the accumulated knowledge be applied to the field of atherosclerosis immunotherapy.

CD68/macrosialin: not just a histochemical marker

“…57 Ultrastructural studies of human atherosclerotic lesions demonstrated that CD68 is mostly located in lysosomes (Figure 3). 58,59 In contrast to macrophages, 59 CD68 is not expressed by dendritic cells (DCs) 14,60 and this helps to immunohistochemically distinguish these two cell types, both of which have antigenpresenting capabilities. Several studies have shown significant upregulation of CD68 expression in macrophages in response to inflammatory stimuli such as exposure to oxLDL 12,49,50 and chronic stimulation with bacterial lipopolysaccharide (LPS) or inflammatory cytokine interferon-γ (IFN-γ).…”

Tolerization against atherosclerosis using heat shock protein 60

“…For example, it has been demonstrated in several studies that T cells are one of the first cells to invade the arterial intima, later followed by macrophages, DCs, and SMCs in predisposed sites (Xu et al 1990;Kleindienst et al 1993;Millonig et al 2002). However, it has been shown that preexisting vascularassociated dendritic cells (VADCs) are presented in the tertiary lymphoid structures in the aortic adventitia at predisposed sites, even before the invasion of T cells (Bobryshev andLord 1996, 1998;Waltner-Romen et al 1998;Millonig et al 2001a, b;Liu et al 2008;Bobryshev 2010;Cybulsky and JongstraBilen 2010). These DCs can function as antigen-presenting cells (APCs) and thereby capture potentially harmful exogenous or autoantigens and present these to T cells and macrophages.…”

Macrophage Polarization in AIDS: Dynamic Interface between Anti-Viral and Anti-Inflammatory Macrophages during Acute and Chronic Infection

“…Inflammatory M1 macrophages are thought to play a role in the progression and instability of atherosclerotic plaques [67], while M2 macrophages are thought to be anti-inflammatory and atheroprotective [68] (Figure 1). However M2 macrophages take up lipids more readily and become foam cells more easily [69] than M1 macrophages.…”