Decrease in Circulating Myeloid Dendritic Cell Precursors in Coronary Artery Disease

Yılmaz, Atilla; Weber, Jana M.; Cicha, Iwona; Stumpf, Christian; Klein, Michael; Raithel, D; Daniel, Werner G.; Garlichs, Christoph D.

doi:10.1016/j.jacc.2006.01.078

Cited by 103 publications

(132 citation statements)

References 53 publications

(80 reference statements)

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“…Shi et al 22 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 −…”

Section: Circulating Dcs: Biomarkers Of Disease?mentioning

confidence: 99%

“…Functions of specific DC subsets (text boxes) have been dissected. Plasmacytoid DCs (pDCs) promote atherosclerosis by a major histocompatibility complex (MHC)II-dependent activation of Th1 cell responses and secretion of interferon (IFN 18,20 DCs can furthermore be detected in the adventitia and in tertiary lymphoid organs (TLOs) that form in the adventitia of aged Apoe −/− mice primarily in the proximal abdominal aorta. TLOs are organized into distinct compartments, including T-and B-cell areas, and harbor cDCs, pDCs, and monocytederived DCs.…”

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confidence: 99%

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Dendritic Cells in Atherosclerosis

Zernecke

2015

ATVB

104

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Abstract-Atherosclerotic vascular disease is driven by chronic inflammation involving both innate and adaptive immune responses. Dendritic cells (DCs) are found in healthy arteries and accumulate in atherosclerotic lesions and engage in diverse pathogenic and protective mechanisms during atherogenesis. DCs contribute to early foam cell formation, regulate lipid metabolism, and control pro-and antiatherosclerotic T-cell responses by multifarious mechanisms. We, here, review the roles of DCs and plasmacytoid DCs in experimental models of atherosclerosis and the approaches to target DCs in therapeutic vaccination strategies. We, furthermore, discuss the evidence of the potential function of DCs in human atherosclerosis, and dissect the efforts to harness DC subsets as biomarkers of disease. Finally, we discuss necessary future steps that will help to understand the specific contribution of bona fide DCs in atherosclerosis to move toward novel therapeutic approaches. On the basis of distinct developmental pathways, cDCs are further segregated into cDCs type 1 (cDC1s), encompassing CD8α + DCs in lymphoid and CD103 + DCs in nonlymphoid tissue, and CD11b + cDC2s. Analyses of the entire transcriptome revealed a core cDC gene signature absent from monocytes/macrophages and pDCs that include the genes Zbtb46 and Ccr7.7 CD8α + /CD103 + cDCs were furthermore revealed to express toll like receptor (Tlr) 3 and Xcr1, and to require the transcription factors BATF3, IRF8, Id2 for their development, whereas the differentiation of CD11b + cDCs is controlled by RELB, RBPJ and IRF4. The transcription factor E2-2/Tcf4 is an essential regulator of pDC development. [6][7][8][9][10][11][12] Both cDCs and pDCs depend on the growth factor fms-like tyrosine kinase 3 ligand (Flt3L), and Flt3L-dependence can serve as a surrogate marker for common DC precursor origin. 6,10 In contrast, macrophage colony-stimulating factor 1 receptor + monocytes that circulate in blood and enter tissues under inflammatory conditions, give rise to macrophages and monocyte-derived DCs. It is currently unclear if monocyte-derived DCs and macrophages constitute two distinct lineages, or if they are instead highly plastic cells that acquire different functional modules in response to microenvironmental cues 10 (Table 1). In humans, pDCs and 2 types of cDCs (previously referred to as myeloid DCs), namely CD1c + and CD141 + DCs are discriminated, which are considered homologs of CD11b + and CD8 + /CD103 + DCs in mice, respectively. 8,21 These DC subsets circulate as precursors or in an immature state in blood (Table 2) and originate from hematopoietic stem cells in the bone marrow via either granulocyte macrophage progenitors or multilymphoid progenitors. Human homologs of murine DC precursors remain unidentified. 14 Similar to mice, DCs can be detected in the arterial intima of healthy young individuals, 32 and increased numbers of DCs are found in atherosclerotic lesions 29 using unspecific markers, such as S100, CD1a, or fascin. However, a detailed analysis of the...

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Section: Circulating Dcs: Biomarkers Of Disease?mentioning

confidence: 99%

mentioning

confidence: 99%

Dendritic Cells in Atherosclerosis

Zernecke

2015

ATVB

104

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“…The emergence of DC precursors in vulnerable plaques suggests their recruitment into atheromata as a possible reason for their decrease in blood. 5 In our previous study, we have found that DC in patients with acute coronary syndrome (ACS) were activated 6 but the precise activation and signalling mechanisms in the pathogenesis of atherosclerosis remain ill defined.…”

Section: Introductionmentioning

confidence: 99%

Toll‐like receptor‐4 and mitogen‐activated protein kinase signal system are involved in activation of dendritic cells in patients with acute coronary syndrome

Wang

Kang

et al. 2008

Immunology

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Summary Atherosclerosis is an inflammatory disease in which dendritic cells have been suggested to play an essential role. The underlying signalling mechanisms are unknown thus far. The family of Toll‐like receptors (TLRs) initiates innate immune responses, and Toll‐like receptor‐4 (TLR4) has been considered to be an important player in the initiation and progression of atherosclerotic disease. The highly conserved mitogen‐activated protein kinase (MAPK) family is one of the major kinase families that regulate cells by transducing extracellular into cellular responses. Three important members of this family are the extracellular signal‐regulated kinase (ERK), p38, and c‐Jun N‐terminal kinase (JNK). The aim of the study was to investigate the expression of TLR4 and MAPK families on dendritic cells (DC) in patients with coronary arteriosclerosis disease. We have examined the expression of TLR4 protein and mRNA by flow cytometry and real‐time quantitative reverse transcription polymerase chain reaction (RT–PCR). In addition, the expression of MAPK family proteins have been determined by Western blot analysis. We examined the expression level of CD80 to value the maturation state of DC. We compared the levels of cytokines in DC in response to lipopolysaccharide (LPS). The results showed that the expression of TLR4 and MAPK families are increased in the patients with acute coronary syndrome (ACS), compared with it in the patients with stable angina and controls. DC in ACS are activated evaluated by its mature marker and cytokine secreting responding to LPS. We suggest that TLR4 and MAPK families maybe involved in activation of circulating DC of ACS patients.

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“…9 Additionally, DCs have been implicated to play an important role in atherosclerosis. 13 Human plaque is occupied by 2 different types of DC, myeloid (mDCs) and plasmacytoid (pDCs) DCs, 14 -16 both highly efficient in regulating plaque inflammation. Plaque-residing mDCs produce T-cell-attracting chemokines and form clusters with activated T cells.…”

mentioning

confidence: 99%