CD73 expression is critical to therapeutic effects of human endometrial regenerative cells in inhibition of cardiac allograft rejection in mice,STEM CELLS Translational Medicine

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CD73 expression is critical to therapeutic effects of human endometrial regenerative cells in inhibition of cardiac allograft rejection in mice
STEM CELLS Translational Medicine ( IF 5.4 ) Pub Date : 2020-10-30 , DOI: 10.1002/sctm.20-0154
Yonghao Hu _{1,

2} , Dejun Kong _{1,

2} , Yafei Qin _{1,

2} , Dingding Yu _{1,

2} , Wang Jin _{1,

2} , Xiang Li _{1,

2} , Yiming Zhao _{1,

2} , Hongda Wang _{1,

2} , Guangming Li _{1,

2} , Jingpeng Hao _{2,

3} , Baoren Zhang _{1,

2} , Zhaoyan Pang ₄ , Hao Wang _{1,

2}

Affiliation

The newly found mesenchymal‐like endometrial regenerative cells (ERCs) have been proved to induce immune tolerance in cardiac allograft transplantation. However, the therapeutic mechanism is not clear. The present study was undertaken to investigate whether ecto‐5′‐nucleotidase (CD73) expression on ERCs is critical to cardiac allograft protection. C57BL/6 mouse recipients receiving BALB/c mouse cardiac allografts were treated with unmodified ERCs or anti‐CD73 monoclonal antibodies (mAb) pretreated ERCs, respectively. It has been found that CD73 expression was critical to ERC‐induced attenuation of graft pathology. The blockage of CD73 expression on ERCs was related to the percentage decline of tolerogenic dendritic cells (Tol‐DCs), macrophages type 2 (M2), and regulatory T cells (Tregs). As compared with anti‐CD73 mAb pretreated ERCs group, CD73 expressing ERCs significantly increased the level of anti‐inflammatory cytokine IL‐10 but decreased levels of pro‐inflammatory cytokines including IFN‐γ and TNF‐α. In addition, CD73 expressing ERCs showed tissue protective function via the regulation of adenosine receptor expression which was related to the infiltration of CD4⁺ and CD8⁺ cells in the allografts. Furthermore, significant increase of A_2B receptors in the cardiac allograft was also associated with CD73 expressing ERC‐induced prolongation of cardiac allograft survival.

中文翻译：

CD73 表达对人子宫内膜再生细胞抑制小鼠心脏同种异体移植排斥的治疗效果至关重要

新发现的间充质样子宫内膜再生细胞（ERCs）已被证明在心脏同种异体移植中诱导免疫耐受。然而，治疗机制尚不清楚。本研究旨在调查 ERC 上的外 5'-核苷酸酶 (CD73) 表达是否对心脏同种异体移植物保护至关重要。接受 BALB/c 小鼠心脏同种异体移植物的 C57BL/6 小鼠受体分别用未修饰的 ERC 或抗 CD73 单克隆抗体 (mAb) 预处理的 ERC 治疗。已经发现，CD73 表达对于 ERC 诱导的移植物病理学衰减至关重要。ERC 上 CD73 表达的阻断与耐受性树突状细胞 (Tol-DCs)、2 型巨噬细胞 (M2) 和调节性 T 细胞 (Tregs) 的百分比下降有关。与抗 CD73 mAb 预处理的 ERC 组相比，表达 CD73 的 ERC 显着增加了抗炎细胞因子 IL-10 的水平，但降低了包括 IFN-γ 和 TNF-α 在内的促炎细胞因子的水平。此外，表达 CD73 的 ERCs 通过调节与 CD4 浸润有关的腺苷受体表达而表现出组织保护功能。^{同种异体移植物中的+}和 CD8 ⁺细胞。此外，心脏同种异体移植物中 A _2B受体的显着增加也与表达 CD73 的 ERC 诱导的心脏同种异体移植物存活时间延长有关。

更新日期：2020-10-30

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