Decreased numbers of peripheral blood dendritic cells in patients with coronary artery disease are associated with diminished plasma Flt3 ligand levels and impaired plasmacytoid dendritic cell function

Brussel, Ilse Van; Vré, Emily A. Van; Meyer, Guido R.Y. De; Vrints, Christiaan J.; Bosmans, Johan; Bult, Hidde

doi:10.1042/cs20100440

Cited by 36 publications

(31 citation statements)

References 51 publications

(76 reference statements)

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“…Other researchers detected decreased numbers of pDCs in patients with troponin-positive unstable coronary artery syndromes (Van Vré et al, 2006), end-stage heart disease (Athanassopoulos et al, 2004), and advanced CAD (Yilmaz et al, 2009; Van Vré et al, 2010). Furthermore, an inverse correlation between the severity of CAD and pDC numbers was observed (Yilmaz et al, 2009; Van Brussel et al, 2011). Decrease in pDC levels observed in acute coronary events could reflect increased recruitment of pDCs in supporting advanced pronflammatory responses preceding the acute cardiovascular event (Sorrentino et al, 2010).…”

Section: Proinflammatory Activities Of Pdcs In Atherosclerosismentioning

confidence: 99%

“…Plaque tissues of patients with ischemic complications (and shoulder regions especially) expressed higher levels of CD83 (Siglec), a marker of DC activation (Erbel et al, 2007). However, Van Brussel et al (2011) showed that pDCs derived from CAD patients expressed lower levels of CD83 and TLR7 and as a consequence produced less IFN-α. Similarly, decreased expression of proinflammatory cytokines (IL-1β and IL-6) was observed in type 2 diabetic patients with atherosclerotic complications (Corrales et al, 2007).…”

Section: Proinflammatory Activities Of Pdcs In Atherosclerosismentioning

confidence: 99%

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Plasmacytoid dendritic cells: development, functions, and role in atherosclerotic inflammation

et al. 2014

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Plasmacytoid dendritic cells (pDCs) are a specialized subset of DCs that links innate and adaptive immunity. They sense viral and bacterial pathogens and release high levels of Type I interferons (IFN-I) in response to infection. pDCs were shown to contribute to inflammatory responses in the steady state and in pathology. In atherosclerosis, pDCs are involved in priming vascular inflammation and atherogenesis through production of IFN-I and chemokines that attract inflammatory cells to inflamed sites. pDCs also contribute to the proinflammatory activation of effector T cells, cytotoxic T cells, and conventional DCs. However, tolerogenic populations of pDCs are found that suppress atherosclerosis-associated inflammation through down-regulation of function and proliferation of proinflammatory T cell subsets and induction of regulatory T cells with potent immunomodulatory properties. Notably, atheroprotective tolerogenic DCs could be induced by certain self-antigens or bacterial antigens that suggests for great therapeutic potential of these DCs for development of DC-based anti-atherogenic vaccines.

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Section: Proinflammatory Activities Of Pdcs In Atherosclerosismentioning

confidence: 99%

Section: Proinflammatory Activities Of Pdcs In Atherosclerosismentioning

confidence: 99%

Plasmacytoid dendritic cells: development, functions, and role in atherosclerotic inflammation

et al. 2014

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“…As DC precursors they are relatively immature and express only low levels of adhesion and costimulatory molecules—at least in physiological conditions [10–12]. mDCs (0.26% among leukocytes) descend from the myeloid lineage, and express blood DC antigen (BDCA)-1 (= CD1c), CD11c, and Toll-like receptors TLR2, TLR4, TLR5, and TLR3 [13–15].…”

Section: Circulating Dcs In Cadmentioning

confidence: 99%

Dendritic Cells in Human Atherosclerosis: From Circulation to Atherosclerotic Plaques

Vré

Brussel

Bosmans

et al. 2011

Mediators of Inflammation

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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.

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“…38 Although these studies have failed to unequivocally identify certain DC subsets as biomarkers of disease, the majority of studies observed a decline in DC numbers in CAD. With a finer delineation of circulating DC subsets/precursors, including CD141…”

Section: Cd11cmentioning

confidence: 99%

Dendritic Cells in Atherosclerosis

Zernecke

2015

ATVB

112

113

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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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Decreased numbers of peripheral blood dendritic cells in patients with coronary artery disease are associated with diminished plasma Flt3 ligand levels and impaired plasmacytoid dendritic cell function

Cited by 36 publications

References 51 publications

Plasmacytoid dendritic cells: development, functions, and role in atherosclerotic inflammation

Plasmacytoid dendritic cells: development, functions, and role in atherosclerotic inflammation

Dendritic Cells in Human Atherosclerosis: From Circulation to Atherosclerotic Plaques

Dendritic Cells in Atherosclerosis

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