SDF-1/CXCR4 axis enhances the immunomodulation of human endometrial regenerative cells in alleviating experimental colitis

SDF-1/CXCR4轴增强人子宫内膜再生细胞的免疫调节作用以缓解实验性结肠炎

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作者:Xiang Li, Xu Lan, Yiming Zhao, Grace Wang, Ganggang Shi, Hongyue Li, Yonghao Hu, Xiaoxi Xu, Baoren Zhang, Kui Ye, Xiangying Gu, Caigan Du, Hao Wang1

Abstract

Endometrial regenerative cells (ERCs) are a new type of mesenchymal-like stromal cells, and their therapeutic potential has been tested in a variety of disease models. SDF-1/CXCR4 axis plays a chemotaxis role in stem/stromal cell migration. The aim of the present study was to investigate the role of SDF-1/CXCR4 axis in the immunomodulation of ERCs on the experimental colitis. The immunomodulation of ERCs in the presence or absence of pretreatment of SDF-1 or AMD3100 was examined in both in vitro cell culture system and dextran sulphate sodium-induced colitis in mice. The results showed that SDF-1 increased the expression of CXCR4 on the surface of ERCs. As compared with normal ERCs, the SDF-1-treated, CXCR4 high-expressing ERCs more significantly suppressed dendritic cell population as well as stimulated both type 2 macrophages and regulatory T cells in vitro and in vivo. Meanwhile, SDF-1-pretreated ERCs increased the generation of anti-inflammatory factors (e.g., IL-4, IL-10) and decreased the pro-inflammatory factors (e.g., IL-6, TNF-α). In addition, SDF-1-pretreated CM-Dil-labeled ERCs were found to engraft to injured colon. Our results may suggest that an SDF-1-induced high level of CXCR4 expression enhances the immunomodulation of ERCs in alleviating experimental colitis in mice.

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