Expression of coinhibitory PD-L1 on CD4+CD25+FOXP3+ regulatory T cells is elevated in patients with acute coronary syndrome

Li, Sihui; Chen, Weijun; Yan, Min; Shu, Yan-Wen; Liao, Yuhua

doi:10.1097/mca.0000000000000282

Cited by 23 publications

(15 citation statements)

References 19 publications

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“…In our study, the serum levels of IL-6, TNF- α , and IFN- γ were significantly higher in ACS patients than in controls, which was in accordance with previous studies [8, 14, 19–21]. As an anti-inflammatory cytokine, the serum IL-4 levels in CAD patients were controversial [22–24]. We found lower levels of IL-4 in AMI patients, as compared with controls and SAP patients.…”

Section: Discussionsupporting

confidence: 91%

Serum Cytokine Profile in Relation to the Severity of Coronary Artery Disease

Min

Liu

et al. 2017

BioMed Research International

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Objectives. To investigate the potential association of a set of serum cytokines with the severity of coronary artery disease (CAD). Methods. A total of 201 patients who underwent coronary angiography for chest discomfort were enrolled. The concentrations of serum IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10, IL-9, and IL-17 were determined by xMAP multiplex technology. The CAD severity was assessed by Gensini score (GS). Results. The serum levels of TNF-α, IL-6, IL-9, IL-10, and IL-17 were significantly higher in high GS group (GS ≥ 38.5) than those in low GS group (GS < 38.5). Positive correlations were also found between these cytokines and the severity of CAD. After adjustment for other associated factors, three serum cytokines (IL-6, IL-9, and IL-17) and two clinical risk factors (creatinine and LDL-C) were identified as the independent predictors of increased severity of CAD. ROC curve analysis revealed that the logistic regression risk prediction model had a good performance on predicting CAD severity. Conclusions. Combinatorial analysis of serum cytokines (IL-6, IL-9, and IL-17) with clinical risk factors (creatinine and LDL-C) may contribute to the evaluation of the severity of CAD and may help guide the risk stratification of angina patients, especially in primary health facilities and in the catheter lab resource-limited settings.

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Section: Discussionsupporting

confidence: 91%

Serum Cytokine Profile in Relation to the Severity of Coronary Artery Disease

Min

Liu

et al. 2017

BioMed Research International

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“…In cardiovascular disease patients, altered levels of circulating PD-1 and PD-L1 expressing cells have been reported ( 16 , 17 ). For example, PD-1 expression on circulating T cells was decreased compared to healthy control individuals and concomitantly, decreased PD-L1 expression on APCs was reported, which corresponded to increased T cell responses ( 18 ).…”

Section: Introductionmentioning

confidence: 99%

Stimulation of the PD-1 Pathway Decreases Atherosclerotic Lesion Development in Ldlr Deficient Mice

Grievink

Smit

Verwilligen

et al. 2021

Front. Cardiovasc. Med.

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Aim: Signaling through the coinhibitory programmed death (PD)-1/PD-L1 pathway regulates T cell responses and can inhibit ongoing immune responses. Inflammation is a key process in the development of atherosclerosis, the underlying cause for the majority of cardiovascular diseases. Dampening the excessive immune response that occurs during atherosclerosis progression by promoting PD-1/PD-L1 signaling may have a high therapeutic potential to limit disease burden. In this study we therefore aimed to assess whether an agonistic PD-1 antibody can diminish atherosclerosis development.Methods and Results: Ldlr−/− mice were fed a western-type diet (WTD) while receiving 100 μg of an agonistic PD-1 antibody or control vehicle twice a week. Stimulation of the PD-1 pathway delayed the WTD-induced monocyte increase in the circulation up to 3 weeks and reduced T cell activation and proliferation. CD4+ T cell numbers in the atherosclerotic plaque were reduced upon PD-1 treatment. More specifically, we observed a 23% decrease in atherogenic IFNγ-producing splenic CD4+ T cells and a 20% decrease in cytotoxic CD8+ T cells, whereas atheroprotective IL-10 producing CD4+ T cells were increased with 47%. Furthermore, we found an increase in regulatory B cells, B1 cells and associated atheroprotective circulating oxLDL-specific IgM levels in agonistic PD-1-treated mice. This dampened immune activation following agonistic PD-1 treatment resulted in reduced atherosclerosis development (p < 0.05).Conclusions: Our data show that stimulation of the coinhibitory PD-1 pathway inhibits atherosclerosis development by modulation of T- and B cell responses. These data support stimulation of coinhibitory pathways as a potential therapeutic strategy to combat atherosclerosis.

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“…Furthermore, T cell population and FOXP3 levels has been shown to be decreased in patients with ACS compared with stable angina and normal coronary arteries patients . Besides, a recent study has shown higher expression of the coinhibitory molecule PD‐L1 on peripheral blood Tregs in patients with ACS compared with chronic coronary artery disease and controls . The observed lower expression of FOXP3 as well as Th17/Treg functional imbalance in patients with ACS have implied a potential role for Th17/Treg disparity in plaque destabilization and the occurrence of ACS .…”

Section: Discussionmentioning

confidence: 91%

“…14 Besides, a recent study has shown higher expression of the coinhibitory molecule PD-L1 on peripheral blood Tregs in patients with ACS compared with chronic coronary artery disease and controls. 15 The observed lower expression of FOXP3 as well as Th17/Treg functional imbalance in patients with ACS have implied a potential role for Th17/Treg disparity in plaque destabilization and the occurrence of ACS. 4 In the present study we evaluated the expression of FOXP3 in ACS as well as the MI and UA subgroups in both sexes.…”

Section: Discussionmentioning

confidence: 99%

Genetic variants and expression study of FOXP3 gene in acute coronary syndrome in Iranian patients

Gholami

Esfandiary

Vatanparast

et al. 2016

Cell Biochemistry & Function

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Considering the role of immune system in different stages of acute coronary syndrome (ACS), we evaluated the expression of FOXP3 gene as a master regulator of immune response in these patients compared with normal subjects. We detected a significant down-regulation of this gene in patients with ACS. Such decreased expression was more prominent in female patients, which implies the role of immune responses in plaque destabilization in such patients.

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Expression of coinhibitory PD-L1 on CD4+CD25+FOXP3+ regulatory T cells is elevated in patients with acute coronary syndrome

Abstract: Expression of the coinhibitory molecule PD-L1 on peripheral blood Tregs is correlated negatively with the severity of CHD and could serve as a novel indicator of ACS.

Cited by 23 publications

References 19 publications

Serum Cytokine Profile in Relation to the Severity of Coronary Artery Disease

Serum Cytokine Profile in Relation to the Severity of Coronary Artery Disease

Stimulation of the PD-1 Pathway Decreases Atherosclerotic Lesion Development in Ldlr Deficient Mice

Genetic variants and expression study of FOXP3 gene in acute coronary syndrome in Iranian patients

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