Corrigendum to: Deficiency of invariant V 14 natural killer T cells decreases atherosclerosis in LDL receptor null mice

Rogers, Leah; Burchat, Sarah; Gage, Jessica; Hasu, Mirela; Thabet, Mohamad; Wilcox, Lindsay; Ramsamy, Tanya A.; Whitman, Stewart C.

doi:10.1093/cvr/cvp042

Cited by 10 publications

(12 citation statements)

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“…27,28 Our study confirms and extends previous studies demonstrating proatherogenic effects of NKT cells. [3][4][5][27][28][29] In contrast to previous studies, which used either CD1d-deficient ApoE Ϫ/Ϫ or LDLR Ϫ/Ϫ mice, we depleted NKT cells by subjecting 3-day-old ApoE Ϫ/Ϫ mice to thymectomy. 30 It should be noted that neonatal thymectomy also depletes naturally occurring Foxp3 ϩ regulatory T cells, 31 and we have confirmed the depletion of these cells in the atherosclerotic lesions of the thymectomised mice (data not shown).…”

Section: Discussionsupporting

confidence: 89%

“…16 There were also no differences in total plasma cholesterol levels as a result of any treatment, consistent with previous findings of a lack of effect of NKT cells on plasma cholesterol levels and plasma lipoprotein (VLDL, LDL, and HDL) profiles. 27,28 Our study confirms and extends previous studies demonstrating proatherogenic effects of NKT cells. [3][4][5][27][28][29] In contrast to previous studies, which used either CD1d-deficient ApoE Ϫ/Ϫ or LDLR Ϫ/Ϫ mice, we depleted NKT cells by subjecting 3-day-old ApoE Ϫ/Ϫ mice to thymectomy.…”

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confidence: 89%

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NKT Cell Subsets Mediate Differential Proatherogenic Effects in ApoE ^−/− Mice

Agrotis

Besra

et al. 2009

ATVB

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Objective-NKT cells promote atherogenesis, but the subtypes responsible have not been identified. We investigated 2 major NKT cell subtypes (CD4 ϩ and DN NKT) in ApoE Ϫ/Ϫ mice rendered NKT cell-deficient by day-3 neonatal thymectomy (3dTx). Methods and Results-Atherosclerosis development was studied in thymectomized ApoEϪ/Ϫ mice fed a high-fat diet with/without adoptively transferred NKT cells. We demonstrate NKT cell deficiency in thymectomized mice and markedly smaller atherosclerotic lesions. The reduction in lesion size was reversed by adoptive transfer of liver-derived NKT cells. Adoptive transfer of CD4ϩ , but not DN NKT cells, into 3dTx ApoE Ϫ/Ϫ mice increased lesion size 2.5-fold. The differential effects were not attributable to differences in homing to developing atherosclerotic lesions. DN NKT cells expressed at least 3-fold higher levels of inhibitory Ly49 receptors (Ly49A, Ly49C/I, and Ly49G2) than CD4 ϩ NKT cells, and lesions expressed large amounts of their MHC class I ligand. In vitro these inhibitory receptors initiated greater effects in DN NKT cells. Culture of each NKT cell subset with TAP-deficient (MHC class I-deficient) dendritic cells and ␣-GalCer led to secretion of similar amounts of proatherogenic cytokines IL-2, IFN-␥, and TNF but, when cultured with MHC class I-positive dendritic cells, CD4ϩ NKT cells secreted more of these cytokines. Conclusions-CD4ϩ NKT cells are responsible for the proatherogenic activity of NKT cells. Expression of inhibitory Ly49 receptors by the subtypes appears responsible for regulating their secretion of proatherogenic cytokines and their differential proatherogenic effects. Key Words: CD4ϩNKT cells Ⅲ atherosclerosis Ⅲ Ly49 Ⅲ cytokines A therosclerosis is a chronic inflammatory disorder that develops at sites of lipid accumulation in large-and medium-sized arteries, which can lead to myocardial infarctions and strokes. The innate and adaptive immune systems are important for atherosclerosis progression with developing lesions being infiltrated by activated T cells and professional antigen presenting cells. 1 Although it has been generally thought that cell-mediated immune responses in atherosclerosis are mostly directed against peptide antigens, 2 recent data indicate that lipid antigens may also be targets of immune responses, particularly those mediated by NKT cells. [3][4][5] Invariant NKT cells are a subset of T lymphocytes that coexpress some NK cell markers and recognize glycolipid antigens in the context of the nonpolymorphic MHC class I-related glycoprotein CD1d. 6,7 NKT cells in mice express semi-invariant T cell receptors (TCRs) with a V␣14-J␣18 ␣-chain preferentially associated with either V␤8.2, V␤7 or V␤2 ␤-chains. 8 On stimulation, these cells have the capacity to secrete large amounts of cytokines, including IFN-␥ and IL-4, and cause bystander activation of other immune cells including NK cells, B cells and CD8 ϩ T-cells. 9,10 Lipid antigens can be presented to NKT cells as a complex with the CD1d molecule. The natural lipid ligands for activa...

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Section: Discussionsupporting

confidence: 89%

supporting

confidence: 89%

NKT Cell Subsets Mediate Differential Proatherogenic Effects in ApoE ^−/− Mice

Agrotis

Besra

et al. 2009

ATVB

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“…155 Altogether, these studies indicate that NKT cells are proatherogenic. However, in 1 study, activation of NKT cells by α-galactosylceramide (combined intraperitoneal and intravenous administration) reduced lesions in a model of collar-induced carotid atherosclerosis in Ldlr -/-mice, whereas no effect was found in Apoe -/-mice.…”

Section: Apoementioning

confidence: 90%

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

Ait‐Oufella

Sage

Mallat

et al. 2014

Circulation Research

173

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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“…Immunohistochemistry staining for macrophages by monocyte/macrophage antibody-2 (MOMA-2) (model MCA519G; Accurate, Westbury, NY) and smooth muscle cell (SMC) ␣-actin (Clone 1AH; Sigma) was performed as previously described. 30,31 Full-length aortas were stained with fat-soluble dye (Sudan IV) and mounted with glycerol gelatin.…”

Section: Tissue Histology and Immunohistochemical Stainingmentioning

confidence: 99%

Naringenin Decreases Progression of Atherosclerosis by Improving Dyslipidemia in High-Fat–Fed Low-Density Lipoprotein Receptor–Null Mice

Mulvihill

Assini

Sutherland

et al. 2010

ATVB

147

104

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Objective-Naringenin is a citrus flavonoid that potently inhibits the assembly and secretion of apolipoprotein B100 -containing lipoproteins in cultured hepatocytes and improves the dyslipidemia and insulin resistance in a mouse model of the metabolic syndrome. In the present study, we used low-density lipoprotein receptor-null mice fed a high-fat diet (Western, TD96125) to test the hypothesis that naringenin prevents atherosclerosis. Methods and Results-Three groups (chow, Western, and Western plus naringenin) were fed ad libitum for 6 months. TheWestern diet increased fasting plasma triglyceride (TG) (5-fold) and cholesterol (8-fold) levels compared with chow, whereas the addition of naringenin significantly decreased both lipids by 50%. The Western-fed mice developed extensive atherosclerosis in the aortic sinus because plaque area was increased by 10-fold compared with chow-fed animals. Quantitation of fat-soluble dye (Sudan IV)-stained aortas, prepared en face, revealed that Western-fed mice also had a 10-fold increase in plaque deposits throughout the arch and in the abdominal sections of the aorta, compared with chow. Atherosclerosis in both areas was significantly decreased by more than 70% in naringenin-treated mice. Consistent with quantitation of aortic lesions, the Western-fed mice had a significant 6-fold increase in cholesterol and a 4-fold increase in TG deposition in the aorta compared with chow-fed mice. Both were reduced more than 50% by naringenin. The Western diet induced extensive hepatic steatosis, with a 10-fold increase in both TG and cholesteryl ester mass compared with chow. The addition of naringenin decreased both liver TG and cholesteryl ester mass by 80%. The hyperinsulinemia and obesity that developed in Western-fed mice was normalized by naringenin to levels observed in chow-fed mice. Conclusion-These in vivo studies demonstrate that the citrus flavonoid naringenin ameliorates the dyslipidemia in Western-fed low-density lipoprotein receptor-null mice, leading to decreased atherosclerosis; and suggests a potential therapeutic strategy for the hyperlipidemia and increased risk of atherosclerosis associated with insulin resistance. Key Words: atherosclerosis Ⅲ naringenin Ⅲ hyperlipidemia Ⅲ insulin resistance Ⅲ obesity A therosclerotic lesions contribute to myocardial infarction and stroke and are responsible for cardiovascular disease developing into a principal cause of death in industrial societies. 1 Major risk factors for atherosclerosis include age, hypertension, diabetes mellitus, smoking, and dyslipidemia. Atherogenic dyslipidemia is characterized by increased plasma concentrations of triglyceride (TG)-rich very low-density lipoprotein (VLDL) and cholesterol-rich LDL and low levels of high-density lipoprotein. Plasma concentrations of apolipoprotein B100 (apoB100)-containing particles directly correlate with plasma cholesterol levels, making a reduction in apoB100 secretion an attractive therapeutic target.The accumulation of cholesteryl ester (CE) within the arterial intima...

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Corrigendum to: Deficiency of invariant V 14 natural killer T cells decreases atherosclerosis in LDL receptor null mice

Cited by 10 publications

References 0 publications

NKT Cell Subsets Mediate Differential Proatherogenic Effects in ApoE ^−/− Mice

NKT Cell Subsets Mediate Differential Proatherogenic Effects in ApoE ^−/− Mice

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

Naringenin Decreases Progression of Atherosclerosis by Improving Dyslipidemia in High-Fat–Fed Low-Density Lipoprotein Receptor–Null Mice

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Corrigendum to: Deficiency of invariant V 14 natural killer T cells decreases atherosclerosis in LDL receptor null mice

Cited by 10 publications

References 0 publications

NKT Cell Subsets Mediate Differential Proatherogenic Effects in ApoE −/− Mice

NKT Cell Subsets Mediate Differential Proatherogenic Effects in ApoE −/− Mice

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

Naringenin Decreases Progression of Atherosclerosis by Improving Dyslipidemia in High-Fat–Fed Low-Density Lipoprotein Receptor–Null Mice

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NKT Cell Subsets Mediate Differential Proatherogenic Effects in ApoE ^−/− Mice

NKT Cell Subsets Mediate Differential Proatherogenic Effects in ApoE ^−/− Mice