Dendritic Cells in Human Atherosclerosis: From Circulation to Atherosclerotic Plaques

Abstract

Background. Atherosclerosis is a chronic inflammatory disease with atherosclerotic plaques containing inflammatory infiltrates predominantly consisting of monocytes/macrophages and activated T cells. More recent is the implication of dendritic cells (DCs) in the disease. Since DCs were demonstrated in human arteries in 1995, numerous studies in humans suggest a role for these professional antigen-presenting cells in atherosclerosis. Aim. This paper focuses on the observations made in blood and arteries of patients with atherosclerosis. In principal, flow cytometric analyses show that circulating myeloid (m) and plasmacytoid (p) DCs are diminished in coronary artery disease, while immunohistochemical studies describe increased intimal DC counts with evolving plaque stages. Moreover, mDCs and pDCs appear to behave differently in atherosclerosis. Yet, the origin of plaque DCs and their relationship with blood DCs are unknown. Therefore, several explanations for the observed changes are postulated. In addition, the technical challenges and discrepancies in the research field are discussed. Future. Future studies in humans, in combination with experimental animal studies will unravel mechanisms leading to altered blood and plaque DCs in atherosclerosis. As DCs are crucial for inducing but also dampening immune responses, understanding their life cycle, trafficking and function in atherosclerosis will determine potential use of DCs in antiatherogenic therapies.

Dendritic Cells in Atherosclerosis

“…27 The mechanisms responsible for the decline in blood DCs in atherosclerosis may include an enhanced recruitment to lymphoid organs or sites of inflammation, as suggested by their accumulation in vulnerable lesions, 20 an increased DC turnover, or a decreased production or release from bone marrow. 37 Interestingly, decreased numbers of blood Lin −…”

Interferons as Essential Modulators of Atherosclerosis

“…The T1 IFN-producing pDCs have also been found in plaques, with a specific localization in its rupture-prone areas. [45][46][47][48] Overall, the role of IFN-γ in atherosclerosis has been investigated thoroughly, 27,28,32,[49][50][51] whereas research on the role of T1 IFNs in atherosclerosis development has only recently started. 26,52,53 Table 2 summarizes important murine atherosclerotic studies on the T1 and T2 IFNs.…”

Tissue-resident dendritic cells and diseases involving dendritic cell malfunction

“…pDCs (0.2% in leukocytes) express BDCA-2 (or CD303) and CD123, and are specialized in antiviral innate immune responses by producing copious amounts of type I interferons (IFN-γ) upon exposure of intracellular TLR9 and TLR7 to DNA and RNA viruses. In addition, a small third population (0.02% of leukocytes) of blood DCs are distinguishable based on the expression of CD11c and BDCA-3 (or CD141), but not BDCA-1, CD123 and BDCA-2 [ 14 ]. Mouse blood DCs are less well characterized with a majority of circulating MHC class II + CD11c + as pDCs and low numbers of MHC class II + CD11c + and MHC class II – CD11c + DC progenitors that give rise to CD8α + and CD8α – DCs in lymphoid organs.…”