Crosstalk between dendritic cells and T lymphocytes during atherogenesis: Focus on antigen presentation and break of tolerance

Abstract

Atherosclerosis is a chronic disease resulting from an impaired lipid and immune homeostasis, where the interaction between innate and adaptive immune cells leads to the promotion of atherosclerosis-associated immune-inflammatory response. Emerging evidence has suggested that this response presents similarities to the reactivity of effector immune cells toward self-epitopes, often as a consequence of a break of tolerance. In this context, dendritic cells, a heterogeneous population of antigen presenting cells, play a key role in instructing effector T cells to react against foreign antigens and T regulatory cells to maintain tolerance against self-antigens and/or to patrol for self-reactive effector T cells. Alterations in this delicate balance appears to contribute to atherogenesis. The aim of this review is to discuss different DC subsets, and their role in atherosclerosis as well as in T cell polarization. Moreover, we will discuss how loss of T cell tolerogenic phenotype participates to the immune-inflammatory response associated to atherosclerosis and how a better understanding of these mechanisms might result in designing immunomodulatory therapies targeting DC-T cell crosstalk for the treatment of atherosclerosis-related inflammation.

Keywords: ApoB; T cell priming; atherosclerosis; break of tolerance; dendritic cells.

FIGURE 1

Illustration of hematopoietic stem cells (HSCs) differentiation to terminal blood and tissue cells. Hematopoietic stem cells (HSCs) generate common lymphoid progenitors (CLPs) and common myeloid progenitors (CMPs). CLPs exit the bone marrow to reach the thymus or the spleen and generate lymphocyte T and lymphocyte B cells respectively. CMPs differentiate to Granulocyte-Macrophage Progenitors (GMPs) which are the precursors of monocyte-DC progenitors (MDPs), and common DC progenitors (CDPs). CDPs mature to preDCs and pDCs in the bloodstream; once in the tissue preDCs differentiate in conventional DCs (cDCs). MDPs mature to monocytes in the blood and once in peripheral tissues give rise to macrophages and also to MoDCs.