Immunity in Atherosclerosis: Focusing on T and B Cells

Poznyak, Anastasia V.; Bezsonov, Evgeny E.; Popkova, T.; Стародубова, А В; Orekhov, Alexander N.

doi:10.3390/ijms22168379

Cited by 25 publications

(21 citation statements)

References 92 publications

(90 reference statements)

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“…Dendritic cells proliferated and activated in the presence of GM-CSF produced by endothelial cells [48], which is consistent with the ndings of this study. Generally, B1 lymphocytes were considered to have a solid ability to resist atherosclerosis plaque formation and play an essential role in reducing foam cells [49]. In this study, the number of activated B cells was signi cantly reduced compared with those in the healthy group, suggesting that the adaptive immune function of the patients was decreased to a certain extent.…”

Section: Animal Subject Validationmentioning

confidence: 55%

Identification of biomarkers and therapeutic targets in the peripheral immune landscape from coronary artery disease

Feng

Zhang

et al. 2022

Preprint

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Background: Although it plays a vital role in the whole process of various cardiovascular diseases, the characteristic immune changes of peripheral blood in patients with CAD have not been well recognized. This study aimed to determine the expression of differentially expressed immune-related genes (DE-IRGs) in CAD by screening three gene chips downloaded from the Gene Expression Omnibus (GEO) database. Methods: We downloaded CAD and Healthy groups’ information and IRGs from the GEO database and Immport database (ImmpDb) respectively. By R software, we processed GO and KEGG analysis to find out the function and main enriched pathway between two groups. LASSO method was used to identify genes for diagnostic testing. CIBERSORT analysis revealed the differential immune cell distribution. Finally, we verified the expression of these differential genes through an animal project.Results: 762 differentially expressed genes (DEGs) were identified in this process, which mainly enriched in infection, immune response and neural activity and might participate in the CAD process by affecting the extracellular matrix formation and receptor-ligand activity functions. In total, 58 DE-IRGs were subsequently obtained by overlapping the DEGs and immune-related genes downloaded from ImmpDb. Through LASSO regression, CCR9, CER1, CSF2, IL13RA1, INSL5, MBL2, MMP9, MSR1, NTS, TNFRSF19, CXCL2, HTR3C, IL1A, and NR4A2 among the 58 DE-IRGs were distinguished as peripheral biomarkers of CAD, which showed eligible diagnostic capabilities separately. These screened genes were then validated by an animal subject. The real-time PCR test showed that CCR9, CSF2, IL13RA1, and NTS had significant differences between the CAD model and healthy control samples, suggesting that they were promising diagnostic and therapeutic targets. Besides, CIBERSORT algorithm analysis showed that the immune-related cells existed characteristic distribution in CAD, which was discovered to have a close relationship with some specific DE-IRGs. Conclusions: In summary, we confirmed four peripheral immune biomarkers related to CAD and provided new potential targets for regulating the immune relevant mechanism, laying a foundation for further excavation of CAD immune mechanism.

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Section: Animal Subject Validationmentioning

confidence: 55%

Identification of biomarkers and therapeutic targets in the peripheral immune landscape from coronary artery disease

Feng

Zhang

et al. 2022

Preprint

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“…T cells, another important immune cell in adaptive immunity, are key modulators of atherosclerosis. T cell subpopulations differ at different stages of atherosclerosis, in both plaque and circulation ( 43 ). Furthermore, different subpopulations of T cells have different effects on atherosclerosis progression through immune activation, immune suppression, or by helping B cells produce antibodies ( 44 ).…”

Section: Discussionmentioning

confidence: 99%

Enlarged Pericarotid Lymph Nodes Suggest Recent Ischemic Symptoms in Patients with Carotid Atherosclerosis

Sun

Wang

et al. 2022

Front. Immunol.

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Atherosclerosis is a chronic inflammatory disease closely associated with immunological activity. Lymph nodes (LNs) are essential secondary lymphoid organs, in which complex immune responses occur. Enlarged LNs are commonly observed around inflamed tissues or tumors; however, their role in atherosclerosis is not well understood. We hypothesized that enlarged pericarotid LNs would be present in symptomatic patients with carotid atherosclerosis. Therefore, we recorded the size of LNs around the carotid artery during surgery in patients undergoing carotid endarterectomy (CEA) for carotid atherosclerotic stenosis. Patients were stratified by enlarged LNs, defined as a diameter ≥ 10mm in the transverse diameters. Demographic and clinical data of participants were measured and analyzed. Hematoxylin and eosin (H&E), Sirius red, DAB-enhanced Perls’ Prussian blue, alizarin red, and immunohistochemistry (IHC) staining were performed for composition identification of plaques or LNs. Symptomatic patients were defined as those presenting with an ipsilateral cerebral ischemic event. Compared with patients with non-enlarged LNs, patients with enlarged LNs were more likely to be symptomatic (22/32, 68.8% versus 9/40, 22.5%, P < 0.001) and use calcium channel blocker drugs (17/32, 53.1% versus 10/40, 25%, P=0.014). In addition, they showed lower body mass index (mean ± SD: 24.00 ± 2.66 versus 25.34 ± 2.56 kg/m2, P=0.034), lower weight (median [interquartile range]: 64 [60.00-76.00] versus 72.5 [65.00-77.50] Kg, P = 0.046) and higher diastolic blood pressure (mean ± SD: 78.94 ± 9.30 versus 73.93 ± 8.84 mmHg, P = 0.022). The plague from patients with enlarged LNs exhibited a lower relative percentage of fibrous tissue (29.49 ± 10.73% versus 34.62 ± 10.33%, P = 0.041). The enlarged LNs remained oval-shaped by visual inspection. Compared to non-enlarged LNs, the predominant changes in enlarged LNs were atrophic lymphatic sinuses and dilated LNs parenchyma. Enlarged LNs contained more germinal centers and lymphocytes. In conclusion, symptomatic patients with carotid atherosclerosis have enlarged pericarotid LNs. The current study supports the conclusion that enlarged LNs with an activated and enhanced adaptive immune response may indicate plaque instability. Pericarotid LNs will be a promising marker of plaque stability and may be a potential therapeutic target in patients with carotid atherosclerosis.

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“…Plaque rupture is a major cause of atherothrombotic events [2]. The infiltration and activation of macrophages and lymphocytes within the atherosclerotic lesion contribute to the plaque instability and subsequent plaque rupture [3]. iNKT cells are an innate-like T lymphocyte that recognize glycolipid antigens presented by the MHC class I-like molecule CD1d and is capable to rapidly and robustly produce a mixture of Th1 and Th2 cytokines, such as IFN-γ and IL-4, leading to subsequent immune responses on activation [4].…”

Section: Discussionmentioning

confidence: 99%

“…Interstitial collagen fibers normally confer the structural stability of the fibrous cap on the plaque. Atherosclerosis results from complex inflammatory processes between hematocytes and vascular tissues [3]. In the early stage of atherosclerosis (characterized by fatty-streak lesions), macrophages and T lymphocytes are frequently found in the atherosclerotic lesions, whereas, in the late stage after progression of atherosclerosis, aggregation of activated macrophages, T lymphocytes, and smooth 2 of 12 muscle cells (SMC) is associated with the development of complex atherosclerotic lesions.…”

Section: Introductionmentioning

confidence: 99%

Natural Killer T Cells Are Involved in Atherosclerotic Plaque Instability in Apolipoprotein-E Knockout Mice

Ohmura

Ishimori

Saito

et al. 2021

IJMS

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The infiltration and activation of macrophages as well as lymphocytes within atherosclerotic lesion contribute to the pathogenesis of plaque rupture. We have demonstrated that invariant natural killer T (iNKT) cells, a unique subset of T lymphocytes that recognize glycolipid antigens, play a crucial role in atherogenesis. However, it remained unclear whether iNKT cells are also involved in plaque instability. Apolipoprotein E (apoE) knockout mice were fed a standard diet (SD) or a high-fat diet (HFD) for 8 weeks. Moreover, the SD- and the HFD-fed mice were divided into two groups according to the intraperitoneal injection of α-galactosylceramide (αGC) that specifically activates iNKT cells or phosphate-buffered saline alone (PBS). ApoE/Jα18 double knockout mice, which lack iNKT cells, were also fed an SD or HFD. Plaque instability was assessed at the brachiocephalic artery by the histological analysis. In the HFD group, αGC significantly enhanced iNKT cell infiltration and exacerbated atherosclerotic plaque instability, whereas the depletion of iNKT cells attenuated plaque instability compared to PBS-treated mice. Real-time PCR analyses in the aortic tissues showed that αGC administration significantly increased expressional levels of inflammatory genes such as IFN-γ and MMP-2, while the depletion of iNKT cells attenuated these expression levels compared to those in the PBS-treated mice. Our findings suggested that iNKT cells are involved in the exacerbation of plaque instability via the activation of inflammatory cells and upregulation of MMP-2 in the vascular tissues.

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Immunity in Atherosclerosis: Focusing on T and B Cells

Cited by 25 publications

References 92 publications

Identification of biomarkers and therapeutic targets in the peripheral immune landscape from coronary artery disease

Identification of biomarkers and therapeutic targets in the peripheral immune landscape from coronary artery disease

Enlarged Pericarotid Lymph Nodes Suggest Recent Ischemic Symptoms in Patients with Carotid Atherosclerosis

Natural Killer T Cells Are Involved in Atherosclerotic Plaque Instability in Apolipoprotein-E Knockout Mice

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