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首页> 外文期刊>Cytokine >Detection of TCD4+ subsets in human carotid atheroma
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Detection of TCD4+ subsets in human carotid atheroma

机译:检测人颈动脉粥样硬化中TCD4 +亚群

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摘要

Activated TCD4+ cells are detected in human atherosclerotic plaques which indicate their participation in disease progression and destabilization. Among these cells, IFN-γ-producing T cells (TH1) are recognized as having a pro-atherogenic role. Recently, the IL-17-producing T helper lineage of cells (TH17) has been identified in atherosclerotic lesions. They have been linked to atheroma development through the production of pro-inflammatory mediators present in these lesions. Furthermore, IL-22 producing TCD4+ cells (TH22) have been identified in the atheromatous environment, but their presence and function has not been investigated. The aim of this study was to analyze the immune response mediated by pro-inflammatory subtypes of TCD4+ cells in atheromatous lesions. Atherosclerotic plaques of 57 patients with critical stenosis of carotid submitted to endarterectomy were evaluated. Three carotid fragments from organ donors were used as control. mRNA analysis showed expression of TH1 (IFN-γ, T-bet, IL-2, IL-12p35, TNF-α and IL-18); TH2 (GATA-3); TH17 (IL-17A, IL-17RA, Rorγt, TGF-β, IL-6, IL-1β, IL-23p19, CCL20, CCR4 and CCR6) and TH22 (IL-22 and Ahr) related markers. Asymptomatic patients showed higher expression of mRNA of IL-10, TGF-β, CCR4 and GATA-3 when compared to symptomatic ones. Immunohistochemistry analysis showed higher levels of IL-23, TGF-β, IL-1β and IL-18 in macrophages and foam cells in unstable lesions compared to stable and control ones. In vitro stimulation of atheroma cells induced IL-17 and IFN-γ production. Finally we were able to detect, the following subpopulations of TCD3+ cells: TCD4+ IFN-γ+, TCD4+IL-17+, TCD4+IL-4+, TCD4+IL-22+ and double positive cells (IFN-γ/IL-17+, IFN-γ/IL-22+ or IL-17/IL-22+). Our results showed the presence of distinct TCD4+ cells subsets in human carotid lesions and suggest that interactions among them may contribute to the atheroma progression and destabilization.
机译:在人的动脉粥样硬化斑块中检测到活化的TCD4 +细胞,表明它们参与了疾病的进展和不稳定。在这些细胞中,产生IFN-γ的T细胞(TH1)被认为具有促动脉粥样硬化作用。最近,在动脉粥样硬化病变中已鉴定出产生IL-17的T辅助细胞系(TH17)。它们通过产生在这些病灶中的促炎性介质与动脉粥样硬化的发展有关。此外,在动脉粥样硬化环境中已鉴定出产生IL-22的TCD4 +细胞(TH22),但尚未研究其存在和功能。这项研究的目的是分析动脉粥样硬化病变中由TCD4 +细胞促炎亚型介导的免疫应答。评价了接受内膜切除术的57例严重颈动脉狭窄患者的动脉粥样硬化斑块。来自器官供体的三个颈动脉片段用作对照。 mRNA分析显示TH1的表达(IFN-γ,T-bet,IL-2,IL-12p35,TNF-α和IL-18); TH2(GATA-3); TH17(IL-17A,IL-17RA,Rorγt,TGF-β,IL-6,IL-1β,IL-23p19,CCL20,CCR4和CCR6)和TH22(IL-22和Ahr)相关标记。与有症状的患者相比,无症状的患者IL-10,TGF-β,CCR4和GATA-3的mRNA表达更高。免疫组织化学分析显示,与稳定和对照相比,不稳定病变中巨噬细胞和泡沫细胞中IL-23,TGF-β,IL-1β和IL-18的水平更高。体外刺激动脉粥样硬化细胞可诱导IL-17和IFN-γ的产生。最后,我们能够检测到以下TCD3 +细胞亚群:TCD4 +IFN-γ+,TCD4 + IL-17 +,TCD4 + IL-4 +,TCD4 + IL-22 +和双阳性细胞(IFN-γ/ IL -17 +,IFN-γ/ IL-22 +或IL-17 / IL-22 +)。我们的结果表明在人的颈动脉病变中存在不同的TCD4 +细胞亚群,并表明它们之间的相互作用可能有助于动脉粥样硬化的进展和不稳定。

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