CD317使TNFR1稳定，并通过NF-κB/TSG6途径赋予间充质干细胞抗炎功能。
CD317 stabilizes TNFR1 and confers the anti-inflammatory functions of MSCs via NF-κB/TSG6 pathway.
作者信息
Chen Si, Yao Lan, Wen Xin, Wang Xianqi, Chen Lin, Zhang Jingting, Xu Jianyong
机构信息
Department of Immunology, Shenzhen University Medical School, Shenzhen University, Shenzhen, 518060, People's Republic of China.
Shenzhen Key Laboratory of Reproductive Immunology for Peri-Implantation, Shenzhen Zhongshan Institute for Reproductive Medicine and Genetics, Shenzhen Zhongshan Obstetrics & Gynecology Hospital, Shenzhen, 518000, People's Republic of China.
出版信息
Stem Cell Res Ther. 2025 Jul 21;16(1):391. doi: 10.1186/s13287-025-04527-8.
BACKGROUND
Although both pre-clinical and clinical studies show promising outcomes, resulting in rapid growth of clinical trials of MSC-based therapies in recent years, the heterogeneity and therapeutic inconsistency of MSCs have severely hampered their clinical applications. Purifying homogenous MSC populations with enhanced specific functions represents one promising approach. We have demonstrated recently that the CD317 MSCs have enhanced anti-inflammatory functions and improved therapeutic efficacy and consistency.
METHODS
In the current study, we performed both in vitro and in vivo investigations to delineate whether and how CD317 regulates the immune modulation function of MSCs.
RESULTS
Our data here indicate that the CD317 directly contributes to the immune suppression function of MSCs stimulated by TNF-α through up-regulating TSG6 via CD317/lipid-raft/TNFR1 complex. The CD317 stabilizes the TNFR1 complex, resulting in hyper-activation of the NF-κB pathway and up-regulation of TSG6, which confers the therapeutic effects of MSCs on the mouse model of ALI (acute lung injury) and IBD (inflammatory bowel disease).
CONCLUSIONS
Thus, the CD317 stabilizes TNFR1 and confers the anti-inflammatory functions of MSCs via NF-κB/TSG6 Pathway.
背景
尽管临床前和临床研究均显示出有前景的结果，使得近年来基于间充质干细胞（MSC）的治疗临床试验迅速增长，但MSC的异质性和治疗不一致性严重阻碍了它们的临床应用。纯化具有增强特定功能的同质MSC群体是一种有前景的方法。我们最近证明，CD317 MSC具有增强的抗炎功能以及改善的治疗效果和一致性。
方法
在当前研究中，我们进行了体外和体内研究，以确定CD317是否以及如何调节MSC的免疫调节功能。
结果
我们的数据表明，CD317通过经由CD317/脂筏/TNFR1复合物上调TSG6，直接促进TNF-α刺激的MSC的免疫抑制功能。CD317使TNFR1复合物稳定，导致NF-κB途径过度激活和TSG6上调，这赋予了MSC对急性肺损伤（ALI）和炎症性肠病（IBD）小鼠模型的治疗效果。
结论
因此，CD317稳定TNFR1并通过NF-κB/TSG6途径赋予MSC抗炎功能。
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