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心力衰竭患者心外膜脂肪组织中的 T 淋巴细胞特征和免疫受体库。

T lymphocyte characteristics and immune repertoires in the epicardial adipose tissue of heart failure patients.

机构信息

Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Front Immunol. 2023 Mar 7;14:1126997. doi: 10.3389/fimmu.2023.1126997. eCollection 2023.

Abstract

BACKGROUND

Epicardial adipose tissue (EAT) acts as an active immune organ and plays a critical role in the pathogenesis of heart failure (HF). However, the characteristics of immune cells in EAT of HF patients have rarely been elucidated.

METHODS

To identify key immune cells in EAT, an integrated bioinformatics analysis was performed on public datasets. EAT samples with paired subcutaneous adipose tissue (SAT), heart, and peripheral blood samples from HF patients were collected in validation experiments. T cell receptor (TCR) repertoire was assessed by high-throughput sequencing. The phenotypic characteristics and key effector molecules of T lymphocytes in EAT were assessed by flow cytometry and histological staining.

RESULTS

Compared with SAT, EAT was enriched for immune activation-related genes and T lymphocytes. Compared with EAT from the controls, activation of T lymphocytes was more pronounced in EAT from HF patients. T lymphocytes in EAT of HF patients were enriched by highly expanded clonotypes and had greater TCR clonotype sharing with cardiac tissue relative to SAT. Experiments confirmed the abundance of IFN-γ effector memory T lymphocytes (T) in EAT of HF patients. CCL5 and GZMK were confirmed to be associated with T lymphocytes in EAT of HF patients.

CONCLUSION

EAT of HF patients was characterized by pronounced immune activation of clonally expanded IFN-γ T and a generally higher degree of TCR clonotypes sharing with paired cardiac tissue.

摘要

背景

心外膜脂肪组织(EAT)作为一个活跃的免疫器官,在心衰(HF)的发病机制中起着关键作用。然而,HF 患者 EAT 中的免疫细胞特征很少被阐明。

方法

为了确定 EAT 中的关键免疫细胞,对公共数据集进行了综合的生物信息学分析。在验证实验中收集了 HF 患者的 EAT 样本,并与配对的皮下脂肪组织(SAT)、心脏和外周血样本进行了比较。通过高通量测序评估 T 细胞受体(TCR)库。通过流式细胞术和组织学染色评估 EAT 中 T 淋巴细胞的表型特征和关键效应分子。

结果

与 SAT 相比,EAT 富含与免疫激活相关的基因和 T 淋巴细胞。与对照组的 EAT 相比,HF 患者的 EAT 中 T 淋巴细胞的激活更为明显。HF 患者的 EAT 中 T 淋巴细胞被高度扩增的克隆型所富集,并且与 SAT 相比,与心脏组织的 TCR 克隆型共享程度更高。实验证实了 HF 患者的 EAT 中 IFN-γ 效应记忆 T 淋巴细胞(T)的丰度。CCL5 和 GZMK 被证实与 HF 患者的 EAT 中的 T 淋巴细胞有关。

结论

HF 患者的 EAT 表现为克隆性扩增的 IFN-γ T 细胞明显的免疫激活,与配对的心脏组织相比,TCR 克隆型的共享程度普遍较高。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b21f/10027920/b0694d727eb6/fimmu-14-1126997-g001.jpg

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