Inhibition of IL-17A in atherosclerosis

Cheng, Xiang; Taleb, Soraya; Wang, Jun; Tang, Tingting; Chen, Jian; Gao, Xingli; Yao, Rui; Xie, Jia‐Zhao; Lei, Yu; Xia, Ni; Yan, Xinxin; Nie, Shaofang; Liao, Mengyang; Cheng, Yan; Mallat, Ziad; Liao, Yuhua

doi:10.1016/j.atherosclerosis.2010.12.034

Cited by 63 publications

(48 citation statements)

References 11 publications

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“…96,97 It is noteworthy that blocking IL-17A in these studies did not alter the signaling pathway, which might be accounted for by the use of polyclonal nonmurine antibodies. On the contrary, blockade of IL-17A with mouse monoclonal anti-IL-17A antibodies that abolished IL-17A signaling did not affect atherosclerosis in Ldlr -/-mice that have low levels of IL-17, 88,98 whereas treatment with rat anti-IL-17A did not abolish IL-17A signaling but reduced atherosclerosis. 98 In Ldlr -/-mice with suppressor of cytokine signaling (SOCS) 3 deletion in T cells, which specifically promotes T-cell polarization toward Th17, IL-17 production was increased and atherosclerosis markedly reduced.…”

Section: Th17 Cellsmentioning

confidence: 81%

“…On the contrary, blockade of IL-17A with mouse monoclonal anti-IL-17A antibodies that abolished IL-17A signaling did not affect atherosclerosis in Ldlr -/-mice that have low levels of IL-17, 88,98 whereas treatment with rat anti-IL-17A did not abolish IL-17A signaling but reduced atherosclerosis. 98 In Ldlr -/-mice with suppressor of cytokine signaling (SOCS) 3 deletion in T cells, which specifically promotes T-cell polarization toward Th17, IL-17 production was increased and atherosclerosis markedly reduced. 88 Interestingly, in these mice, anti-IL-17A treatment with a mouse monoclonal antibody not only blocked the beneficial effect of Th17 polarization but also accelerated atherosclerosis beyond that in WT Ldlr -/-mice.…”

Section: Th17 Cellsmentioning

confidence: 81%

See 1 more Smart Citation

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

Ait‐Oufella

Sage

Mallat

et al. 2014

Circulation Research

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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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Section: Th17 Cellsmentioning

confidence: 81%

Section: Th17 Cellsmentioning

confidence: 81%

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

Ait‐Oufella

Sage

Mallat

et al. 2014

Circulation Research

Self Cite

173

121

View full text Add to dashboard Cite

show abstract

“…Data on the frequency of Th17 cells or IL-17 in the blood of patients with ACS or acute myocardial infarction also provide an unclear message (45)(46)(47)(48)(49)(50). Several murine studies support a proinflammatory, proatherogenic role for the IL-17/IL-17 receptor axis (51)(52)(53)(54)(55)(56), but others failed to find IL-17 to be proatherogenic, and some even found it to be atheroprotective (43,(57)(58)(59). Manipulations of mice that indirectly enhanced Th17 differentiation, including genetic deletion of suppressor of cytokine signaling 3 (Socs3) or anti-CD20-mediated B cell depletion, were atheroprotective (43,60).…”

Section: Figurementioning

confidence: 99%

Adaptive immunity in atherogenesis: new insights and therapeutic approaches

Lichtman¹,

Binder²,

Tsimikas³

et al. 2013

J. Clin. Invest.

172

171

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Many remarkable advances have improved our understanding of the cellular and molecular events in the pathogenesis of atherosclerosis. Chief among these is the accumulating knowledge of how the immune system contributes to all phases of atherogenesis, including well-known inflammatory reactions consequent to intimal trapping and oxidation of LDL. Advances in our understanding of the innate and adaptive responses to these events have helped to clarify the role of inflammation in atherogenesis and suggested new diagnostic modalities and novel therapeutic targets. Here we focus on recent advances in understanding how adaptive immunity affects atherogenesis.

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“…Interestingly, it has been shown in a recent study that IL-17A neutralization by a rat anti-mouse IL-17A antibody reduced atherosclerosis in apoE Ϫ/Ϫ mice without any evidence of reduced IL-17A signaling. 85 Contrariwise, treatment with a mouse anti-IL-17A antibody did not affect atherosclerosis but inhibited IL-17A signaling. A more detailed discussion about the possible reasons for the discrepancy between our study and others is presented in Taleb et al 77 In humans, increased expression of IL-17A, IL-21, and IL-23 has been reported in atherosclerotic lesions from symptomatic patients, as com-pared with asymptomatic patients.…”

Section: Il-17 and Th17 Cellsmentioning

confidence: 99%