Immunomodulatory effects of mesenchymal stromal cells-derived exosome
Immunomodulatory effects of mesenchymal stromal cells-derived exosome
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间充质基质细胞来源的外泌体的免疫调节作用
DOI：
10.1007/s12026-016-8798-6
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发表时间：
2016-08-01
影响因子：
4.4
通讯作者：
Xiao, Yang
中科院分区：
文献类型：
--
作者：
Chen, Wancheng;Huang, Yukai;Xiao, Yang
间充质基质细胞（mesenchymal stromal cells，MSCs）的免疫调节机制尚不清楚。最近的研究表明，骨髓间充质干细胞的免疫调节作用主要是由旁分泌因子介导的。其中，外泌体被认为在间充质干细胞与靶组织之间的通讯中起主要作用。本研究的目的是探讨MSC来源的exosome对外周血单个核细胞（PBMC），特别是T细胞的影响。我们发现，从健康供体骨髓中提取的MSC源性外泌体在体外培养过程中抑制了促炎因子TNF-α和IL-1β的分泌，但增加了抗炎因子TGF-β的浓度。此外，外泌体可诱导1型T辅助细胞（Th 1）转化为2型T辅助细胞（Th 2），并降低T细胞分化为产生白细胞介素17的效应T细胞（Th 17）的潜力。此外，调节性T细胞（Treg）和细胞毒性T淋巴细胞相关蛋白4的水平也增加。这些结果表明，MSC衍生的外泌体具有免疫调节特性。但对PBMC和CD 3 + T细胞的增殖无明显影响，但可促进其凋亡。此外，吲哚胺2，3-双加氧酶（IDO）先前被证明介导MSC的免疫调节，其在与MSC共培养的PBMC中增加。在我们的研究中，IDO显示暴露于MSC衍生的外泌体的PBMC没有显著变化。我们的结论是，外泌体和骨髓间充质干细胞可能在其免疫调节活性和机制不同。
The mechanisms underlying immunomodulatory ability of mesenchymal stromal cells (MSCs) remain unknown. Recently, studies suggested that the immunomodulatory activity of MSCs is largely mediated by paracrine factors. Among which, exosome is considered to play a major role in the communication between MSCs and target tissue. The aim of our study is to investigate the effect of MSCs-derived exosome on peripheral blood mononuclear cells (PBMCs), especially T cells. We find that the MSCs-derived exosome extracted from healthy donors’ bone marrow suppressed the secretion of pro-inflammatory factor TNF-α and IL-1β, but increased the concentration of anti-inflammatory factor TGF-β during in vitro culture. In addition, exosome may induce conversion of T helper type 1 (Th1) into T helper type 2 (Th2) cells and reduced potential of T cells to differentiate into interleukin 17-producing effector T cells (Th17). Moreover, the level of regulatory T cells (Treg) and cytotoxic T lymphocyte-associated protein 4 were also increased. These results suggested that MSC-derived exosome possesses the immunomodulatory properties. However, it showed no effects on the proliferation of PBMCs or CD3+ T cells, but increases the apoptosis of them. In addition, indoleamine 2, 3-dioxygenase (IDO) was previously shown to mediate the immunoregulation of MSCs, which was increased in PBMCs co-cultured with MSCs. In our study, IDO showed no significant changes in PBMCs exposed to MSCs-derived exosome. We conclude that exosome and MSCs might differ in their immune-modulating activities and mechanisms.