oxLDL uptake by dendritic cells induces upregulation of scavenger-receptors, maturation and differentiation

Nickel, Thomas; Schmauß, Daniel; Hanssen, Henner; Sicic, Zelka; Krebs, Bjarne; Jankl, Sarika; Summo, Claudia; Fraunberger, Peter; Walli, Autar K.; Pfeiler, Susanne; Weis, Michael

doi:10.1016/j.atherosclerosis.2009.01.002

Cited by 95 publications

(93 citation statements)

References 43 publications

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“…Since ApoE is expressed at appreciable levels in the skin, it can be speculated that its absence can lead to the accumulation of lipids, which would otherwise be exported to the liver by ApoE through the process of reverse cholesterol transport. It has been demonstrated that hyperlipidemia can affect DC maturation while retaining DC antigen processing and presentation capacity to prime T cells (39)(40)(41). Indeed, the expression of CD86 is increased in dermal DCs of hCD1Tg HJ1Tg Apoe -/-mice.…”

Section: Discussionmentioning

confidence: 98%

“…It has been demonstrated that hyperlipidemia can change DC maturation and thus function (39)(40)(41). To test the possibility that alterations in DC function can lead to the heightened production of IL-17A by HJ1 T cells, we isolated DCs from the LNs of hCD1Tg, hCD1Tg Apoe -/-, and Apoe -/-mice and incubated them with either normal mouse serum from C57BL/6 mice or hyperlipidemic serum from Apoe -/-mice.…”

Section: Hyperlipidemic Serum Enhanced Il-6 Secretion By Dcs and Incrmentioning

confidence: 99%

See 1 more Smart Citation

CD1b-autoreactive T cells contribute to hyperlipidemia-induced skin inflammation in mice

Bagchi¹,

Hé²,

Zhao³

et al. 2017

Journal of Clinical Investigation

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Section: Discussionmentioning

confidence: 98%

Section: Hyperlipidemic Serum Enhanced Il-6 Secretion By Dcs and Incrmentioning

confidence: 99%

CD1b-autoreactive T cells contribute to hyperlipidemia-induced skin inflammation in mice

Bagchi¹,

Hé²,

Zhao³

et al. 2017

Journal of Clinical Investigation

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“…247,248 In vitro, oxLDL strongly modifies human DC phenotype with an upregulation of surface T-cellstimulatory molecules (CD40, CD86, and HLA-DR), scavenger receptor expression (CD36), and increased cytokine production. 249,250 Systemically, however T-cell responses to exogenous immunization were not changed in hypercholesterolemic conditions. 251 DC and MHCII colocalization 252 and frequent contacts between DCs and T cells observed within the…”

Section: Functional Roles For Dcs In Atherosclerosismentioning

confidence: 99%

Adaptive (T and B Cells) Immunity and Control by Dendritic Cells in Atherosclerosis

Ait‐Oufella

Sage

Mallat

et al. 2014

Circulation Research

168

121

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14 Altogether, these early observations on the presence of T cells in human and in mouse atherosclerotic plaques remained associative and did not show causation.Subsequent studies using animal models of atherosclerosis, especially Apoe -/-or Ldlr -/-mice, in which human-like atherosclerotic lesions develop spontaneously or in response to high-fat diet, provided more direct evidence for the participation of adaptive immunity in atherogenesis. Apoe -/-or Ldlr -/-mice crossed with immunodeficient mice that lack the V(D)J recombination-activating protein 1 (Rag1) or have a severe combined immunodeficiency mutation (SCID; scid/scid mice) show, in general, reduced development of atherosclerotic lesions when fed a chow diet.5 These immunodeficient mice that lack both T and conventional B cells are not particularly informative on the role of specific T-and B-cell subpopulations that can be either pro-or antiatherogenic (see below). One study found no difference between immune-competent and immune-deficient mice fed a high-fat diet. 15The specific role of T cells was substantiated by experiments showing that the transfer of CD4 + T cells into scid/scid/ Apoe -/-mice fully reversed the atheroprotection provided by T/B deficiency. 16 However, when the effect of CD4 + T cells was evaluated in CD4-deficient Apoe -/-mice, contrasting results were reported. Female CD4 -/-Apoe -/-mice exhibited markedly larger lesions in the descending thoracic aorta, but no effect was observed in the aortic root when compared with wild-type (WT) Apoe -/-mice. 17 Intriguingly, in a subsequent study using the same CD4/Apoe double knockout mice, atherosclerosis in the aortic sinus was reduced, but the authors made no mention of the effect of CD4 + T-cell deficiency on atherosclerosis in the aorta.18 Of note, in both studies, the CD8 + cell population and the titers of anti-malondialdehyde (MDA)-oxidized lowdensity lipoprotein (oxLDL) IgM antibodies were increased. CD8 + T cells were recently shown to promote the development of vulnerable atherosclerotic plaques, 19 whereas natural antioxLDL IgM autoantibodies are atheroprotective 20 (see below). The specific recognition of peptide antigens presented by MHC molecules triggers TCR signaling, but costimulatory and coinhibitory receptors on T cells direct T-cell function and determine T-cell fate. These cosignaling molecules are members of the immunoglobulin superfamily, including B7 (CD80/86), CD28, programmed cell death 1 and cytotoxic T-lymphocyte antigen 4 (CTLA4), and the tumor necrosis factor (TNF) receptor superfamily, including CD40, CD27, OX40, and CD137. Experiments aimed at investigating the role of cosignaling molecules provided further evidence for a role of T cells in atherogenesis 21,22 (see Functional roles for DCs in atherosclerosis section of this article). For example, blockade of the OX40-OX40L interaction by anti-OX40L antibody treatment in Ldlr -/-23 or Apoe -/-24 mice reduced atherosclerosis. Yet, blockade of T-cell activation was accompanied by an enhanced B-1 cell activity an...

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“…121 Antigens, such as oxLDL and HSPs, bind to TLRs and to scavenger receptors. 13,15,115,123,124 The formation of oxLDL and otherwise modified LDL and their accumulation in the arterial intima are key events in atherosclerosis. 108 From the very early stages of atherosclerotic alteration, the arterial intima represents a vicinity of increased coaccumulation of oxLDL and DCs.…”

Section: Tissue Microenvironment In Atherosclerosis and DC Functionmentioning

confidence: 99%

Dendritic cells and their role in atherogenesis

Bobryshev

2010

Laboratory Investigation

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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.

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oxLDL uptake by dendritic cells induces upregulation of scavenger-receptors, maturation and differentiation

Cited by 95 publications

References 43 publications

CD1b-autoreactive T cells contribute to hyperlipidemia-induced skin inflammation in mice

CD1b-autoreactive T cells contribute to hyperlipidemia-induced skin inflammation in mice

Adaptive (T and B Cells) Immunity and Control by Dendritic Cells in Atherosclerosis

Dendritic cells and their role in atherogenesis

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