Extracellular Vesicles Secreted by TDO2-Augmented Fibroblasts Regulate Pro-inflammatory Response in Macrophages.

Extracellular Vesicles Secreted by TDO2-Augmented Fibroblasts Regulate Pro-inflammatory Response in Macrophages.
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DOI:
10.3389/fcell.2021.733354
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发表时间:
2021
影响因子:
5.5
通讯作者:
Ibrahim AG
Ibrahim AG
中科院分区:
生物学2区
文献类型:
--
作者:
Peck KA;Ciullo A;Li L;Li C;Morris A;Marbán E;Ibrahim AG

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细胞外囊泡(EV)是介导细胞与细胞通讯的分泌型脂质双层囊泡,并且是细胞治疗的效应器。先前的工作已经表明,典型的Wnt信号传导是细胞和EV治疗效力所必需的。色氨酸2,3-双加氧酶(Tryptophan 2,3-dioxygenase,TDO 2)是经典Wnt信号转导的靶基因。在治疗惰性成纤维细胞中增加TDO 2赋予其EV免疫调节能力,包括减弱巨噬细胞中的炎症信号传导。转录组学分析表明,与对照成纤维细胞EV相比,用过表达TDO 2的成纤维细胞EV处理的巨噬细胞具有减弱的炎症反应。在体内,来自TDO 2过表达成纤维细胞的EV保留了心脏功能。总之,这些结果描述了一个主要的典型Wnt靶基因(TDO 2)在驱动细胞及其EV的治疗效力中的作用。
Extracellular vesicles (EVs) are secreted lipid bilayer vesicles that mediate cell to cell communication and are effectors of cell therapy. Previous work has shown that canonical Wnt signaling is necessary for cell and EV therapeutic potency. Tryptophan 2,3-dioxygenase (TDO2) is a target gene of canonical Wnt signaling. Augmenting TDO2 in therapeutically inert fibroblasts endows their EVs with immunomodulatory capacity including attenuating inflammatory signaling in macrophages. Transcriptomic analysis showed that macrophages treated with EVs from fibroblasts overexpressing TDO2 had blunted inflammatory response compared to control fibroblast EVs. In vivo, EVs from TDO2-overexpressing fibroblasts preserved cardiac function. Taken together, these results describe the role of a major canonical Wnt-target gene (TDO2) in driving the therapeutic potency of cells and their EVs.
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