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动脉粥样硬化患者中白细胞介素-10 B细胞的低频率与炎症状态相关。

Low frequency of IL-10 B cells in patients with atherosclerosis is related with inflammatory condition.

作者信息

Rincón-Arévalo Héctor, Quintero Julio C, Fortich Fernando, Rojas Mauricio, Vásquez Gloria, Castaño Diana, Yassin Lina M

机构信息

Grupo de Inmunología Celular e Inmunogenética, Instituto de Investigaciones Médicas, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70-52-21, Medellín, Colombia.

Unidad Cardiovascular, Hospital San Vicente Fundación, Colombia.

出版信息

Heliyon. 2020 Mar 3;6(3):e03441. doi: 10.1016/j.heliyon.2020.e03441. eCollection 2020 Mar.

Abstract

BACKGROUND AND AIMS

B cells involvement in animal models of atherosclerosis has been unequivocally established. However, the role of these cells in patients with atherosclerosis is almost unknown. Besides the production of antibodies, B cells can also exhibit regulatory functions mainly through IL-10. Here, we characterized human B cell subsets, their production of IL-10 in patients with atherosclerosis and their potential association with inflammation.

METHODS

Patients with confirmed atherosclerotic events and controls with low cardiovascular risk were included. B cells subsets were determined in mononuclear cells (PBMC) using flow cytometry. PBMC were cultured (5 h) and (48 h) to determine IL-10 B cells and in some cases TNF-α and IFN-γ CD4 T cells. The inflammatory state of the participants was determined through high sensitivity C reactive protein levels.

RESULTS

Increase in percentage and number of plasmablasts was observed in patients with atherosclerosis compared with controls. A decreased frequency of IL-10 B cells was observed in patients, both in and cultures. This decrease was detected in transitional, memory, and plasmablast subsets. Interestingly, the reduction of IL-10 B cells negatively and significantly correlated with the inflammatory condition of the studied subjects and associated with an increased frequency of TNF-α and IFN-γ CD4 T cells. The blockade of IL-10R did not show further effect in T cells activation.

CONCLUSIONS

There is an association between the inflammatory state and a reduction of IL-10 B cells that could contribute to the development of atherosclerosis.

摘要

背景与目的

B细胞参与动脉粥样硬化动物模型已得到明确证实。然而,这些细胞在动脉粥样硬化患者中的作用几乎未知。除了产生抗体外,B细胞还可主要通过白细胞介素-10发挥调节功能。在此,我们对人类B细胞亚群进行了表征,研究了其在动脉粥样硬化患者中白细胞介素-10的产生情况及其与炎症的潜在关联。

方法

纳入确诊有动脉粥样硬化事件的患者以及心血管风险较低的对照组。使用流式细胞术测定单核细胞(外周血单个核细胞)中的B细胞亚群。培养外周血单个核细胞(5小时)和(48小时)以测定产生白细胞介素-10的B细胞,在某些情况下还测定肿瘤坏死因子-α和干扰素-γ CD4 T细胞。通过高敏C反应蛋白水平确定参与者的炎症状态。

结果

与对照组相比,动脉粥样硬化患者中浆母细胞的百分比和数量增加。在患者中,无论是在5小时培养还是48小时培养中,产生白细胞介素-10的B细胞频率均降低。在过渡型、记忆型和浆母细胞亚群中均检测到这种降低。有趣的是,产生白细胞介素-10的B细胞减少与研究对象的炎症状态呈负相关且具有显著相关性,并与肿瘤坏死因子-α和干扰素-γ CD4 T细胞频率增加相关。白细胞介素-10受体的阻断在T细胞激活中未显示出进一步的作用。

结论

炎症状态与产生白细胞介素-10的B细胞减少之间存在关联,这可能有助于动脉粥样硬化的发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ae5/7057201/f40c86deadd0/gr1.jpg

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