期刊
JOURNAL OF EXTRACELLULAR VESICLES
卷 10, 期 4, 页码 -出版社
WILEY
DOI: 10.1002/jev2.12067
关键词
acute graft-versus-host disease; PD-L1; small extracellular vesicles; T cell receptor; Wharton's Jelly-derived mesenchymal stem cells
类别
资金
- NIGMS [P20GM130423]
- University of Kansas Cancer Center Support [P30CA168524]
Research shows that MSCs derived from Wharton's Jelly secrete sEVs enriched in PD-L1, which play an immunomodulatory role by inhibiting T cell activation. Clinical data suggest that sEV-associated PD-L1 not only predicts outcomes from WJMSC therapy, but also has the potential for developing cell-independent therapies for aGvHD patients.
Both mesenchymal stem cells (MSCs) and their corresponding small extracellular vesicles (sEVs, commonly referred to as exosomes) share similar immunomodulatory properties that are potentially beneficial for the treatment of acute graft versus host disease (aGvHD). We report that clinical grade Wharton's Jelly-derived MSCs (WJMSCs) secrete sEVs enriched in programmed death-ligand 1 (PD-L1), an essential ligand for an inhibitory immune checkpoint. A rapid increase in circulating sEV-associated PD-L1 was observed in patients with aGvHD and was directly associated with the infusion time of clinical grade WJMSCs. In addition, in vitro inhibitory antibody mediated blocking of sEV-associated PD-L1 restored T cell activation (TCA), suggesting a functional inhibitory role of sEVs-PD-L1. PD-L1-deficient sEVs isolated from WJMSCs following CRISPR-Cas9 gene editing fail to inhibit TCA. Furthermore, we found that PD-L1 is essential for WJMSC-derived sEVs to modulate T cell receptors (TCRs). Our study reveals an important mechanism by which therapeutic WJMSCs modulate TCR-mediated TCA through sEVs or sEV-carried immune checkpoints. In addition, our clinical data suggest that sEV-associated PD-L1 may be not only useful in predicting the outcomes from WJMSC clinical administration, but also in developing cell-independent therapy for aGvHD patients.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据