Myeloid-derived suppressor cells are essential for maintaining feto-maternal immunotolerance via STAT3 signaling in mice
Myeloid-derived suppressor cells are essential for maintaining feto-maternal immunotolerance via STAT3 signaling in mice
复制标题
骨髓源性抑制细胞对于通过 STAT3 信号传导维持小鼠母胎免疫耐受至关重要
DOI：
10.1189/jlb.1a1015-481rr
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发表时间：
2016-09-01
影响因子：
5.5
通讯作者：
Zhou, Jie
中科院分区：
文献类型：
--
作者：
Pan, Ting;Liu, Yufeng;Zhou, Jie
MDSC有助于维持胎儿-母体耐受; STAT 3信号转导介导妊娠中P4对MDSC的影响。母体免疫系统对半同种异体胎儿的耐受性对于成功妊娠至关重要;然而，这种免疫耐受性的机制尚未完全阐明。在这里，我们证明了髓源性抑制细胞在维持胎儿-母体耐受性中起着重要作用。在妊娠小鼠的多个免疫器官和蜕膜组织中观察到粒细胞骨髓源性抑制细胞的显著扩增。妊娠来源的粒细胞骨髓来源的抑制细胞以活性氧依赖的方式抑制T细胞反应，并需要直接的细胞-细胞接触。机制研究表明，孕酮促进粒细胞髓源性抑制细胞的分化和激活，通过STAT 3信号转导介导。STAT 3抑制剂JSI-124和特异性短发夹RNA完全消除了孕酮对粒细胞髓源性抑制细胞的影响。更重要的是，粒细胞髓源性抑制细胞耗竭显着提高流产率在正常妊娠小鼠，而过继转移粒细胞髓源性抑制细胞明显降低流产率在CBA/J X DBA/2 J小鼠模型的自然流产。这些观察结果共同表明，粒细胞髓源性抑制细胞在维持小鼠胎儿免疫耐受性中发挥重要作用。此外，我们的研究支持的概念，除了他们的公认的作用，在病理条件下，髓源性抑制细胞在某些生理情况下执行重要的功能。
MDSCs contribute to maintaining feto-maternal tolerance; STAT3 signaling mediates the effects of P4 on MDSCs in pregnancy. Maternal immune system tolerance to the semiallogeneic fetus is essential for a successful pregnancy; however, the mechanisms underlying this immunotolerance have not been fully elucidated. Here, we demonstrate that myeloid-derived suppressor cells play an important role in maintaining feto-maternal tolerance. A significant expansion of granulocytic myeloid-derived suppressor cells was observed in multiple immune organs and decidual tissues from pregnant mice. Pregnancy-derived granulocytic myeloid-derived suppressor cells suppressed T cell responses in a reactive oxygen species-dependent manner and required direct cell-cell contact. Mechanistic studies showed that progesterone facilitated differentiation and activation of granulocytic myeloid-derived suppressor cells, mediated through STAT3 signaling. The STAT3 inhibitor JSI-124 and a specific short hairpin RNA completely abrogated the effects of progesterone on granulocytic myeloid-derived suppressor cells. More importantly, granulocytic myeloid-derived suppressor cell depletion dramatically enhanced the abortion rate in normal pregnant mice, whereas adoptive transfer of granulocytic myeloid-derived suppressor cells clearly reduced the abortion rate in the CBA/J X DBA/2J mouse model of spontaneous abortion. These observations collectively demonstrate that granulocytic myeloid-derived suppressor cells play an essential role in the maintenance of fetal immunotolerance in mice. Furthermore, our study supports the notion that in addition to their well-recognized roles under pathologic conditions, myeloid-derived suppressor cells perform important functions under certain physiologic circumstances.