Interferon-γ and tumor necrosis factor-α promote the ability of human placenta-derived mesenchymal stromal cells to express programmed death ligand-2 and induce the differentiation of CD4+interleukin-10+ and CD8+interleukin-10+Treg subsets
Interferon-γ and tumor necrosis factor-α promote the ability of human placenta-derived mesenchymal stromal cells to express programmed death ligand-2 and induce the differentiation of CD4+interleukin-10+ and CD8+interleukin-10+Treg subsets
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干扰素-γ和肿瘤坏死因子-α促进人胎盘源间充质基质细胞表达程序性死亡配体-2并诱导CD4( )interleukin-10( )和CD8( )interleukin-10( )Treg分化的能力
DOI：
10.1016/j.jcyt.2015.07.018
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发表时间：
2015-11-01
期刊：
影响因子：
4.5
通讯作者：
Luan, Xiying
中科院分区：
文献类型：
--
作者：
Li, Heng;Wang, Weiwei;Luan, Xiying
背景目标。间充质基质细胞（MSC）和调节性T细胞（Treg）已成功用于治疗伴有大量炎性细胞因子如干扰素（IFN）-γ和肿瘤坏死因子（TNF）-α的自身免疫性疾病。因此，本研究探讨了IFN-γ和TNF-α对人胎盘间充质基质细胞（hPMSCs）诱导CD 4（+）白细胞介素（IL）-10（+）和CD 8（+）1 L-10（+）Treg亚群分化能力的影响。方法.分别在存在或不存在trans-well系统或抗程序性死亡配体-2（PDL 2）单克隆抗体（mAb）的情况下，将人PMSC与T细胞共培养。在此基础上检测CD 4（+）IL-10（+）和CD 8（+）IL-10（+）Treg亚群，以及培养上清中IL-10水平。进行检查以探索IFN-γ和TNF-α对hPMSC中PDL 2表达的影响。采用流式细胞术、Western blot和逆转录聚合酶链反应等方法进行检测。结果在hPMSC存在下，来自未活化或通过使用植物血凝素（PHA）或CD 3/CD 28 mAb活化的T细胞的CD 4（+）IL-10（+）和CD 8（+）IL-10（+）Treg亚群显著增加。然而，这些水平显着降低后，在hPMSCs中的PDL 2的表达被阻断。IL-10遵循相同的模式。此外，在trans-well系统中，CD 4（+）IL-10（+）和CD 8（+）IL-10（+）T细胞的百分比也急剧下降，而在IFN-γ和TNF-α预刺激后，hPMSC中的百分比和PDL 2的表达相反地增加。IFN-γ可部分通过JAK/STAT信号通路促进PDL 2的表达。结论. IFN-γ和TNF-α可促进hPMSCs诱导CD 4（+）IL-10（+）和CD 8（+）1 L-10（+）Treg亚群分化的能力，并增强hPMSCs中PDL 2的表达。这将有利于hPMSC在临床试验中的应用。
Background aims. Mesenchymal stromal cells (MSCs) and regulatory T cells (Treg) have been successfully used in treating autoimmune diseases accompanied by abundant inflammatory cytokines such as interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha. Therefore, this work investigated the effects of IFN-gamma and TNF-alpha on the ability of human placenta-derived mesenchymal stromal cells (hPMSCs) on inducing the differentiation of CD4(+)interleukin (IL)-10(+) and CD8(+)1L-10(+)Treg subsets. Methods. Human PMSCs were co-cultured with T cells in the presence or absence of a trans-well system or anti-programmed death ligand-2 (PDL2) monoclonal antibody (mAb), respectively. CD4(+)IL-10(+) and CD8(+)IL-10(+)Treg subsets, as well as the levels of IL-10 in the supernatants, were detected on this basis. Examinations were conducted to explore the impact of IFN-gamma and TNF-alpha on the expression of PDL2 in hPMSCs. In this process, flow cytometry, Western blot and reverse-transcriptase polymerase chain reaction were used. Results. CD4(+)IL-10(+) and CD8(+)IL-10(+)Treg subsets from T cells either non-activated or activated by use of phytohaemagglutinin (PHA) or CD3/CD28mAb significantly increased in the presence of hPMSCs. However, these levels markedly decreased after blocking the expression of PDL2 in hPMSCs. IL-10 followed the same pattern. Furthermore, the percentages of CD4(+)IL-10(+)and CD8(+)IL-10(+)T cells also sharply declined under the trans-well system, whereas the percentages as well as the expression of PDL2 in hPMSCs oppositely raised after hPMSCs pre-stimulated by IFN-gamma and TNF-alpha. IFN-gamma could promote the expression of PDL2 partly through the JAK/STAT signaling pathway. Conclusions. IFN-gamma and TNF-alpha could promote the ability of hPMSCs in inducing the differentiation of CD4(+)IL-10(+)and CD8(+)1L-10(+)Treg subsets and enhance the expression of PDL2 in hPMSCs. These would benefit the application of hPMSCs in clinical trials.