Decidual RANKL/RANK interaction promotes the residence and polarization of TGF-β1-producing regulatory γδ T cells
Decidual RANKL/RANK interaction promotes the residence and polarization of TGF-β1-producing regulatory γδ T cells
复制标题
蜕膜 RANKL/RANK 相互作用促进产生 TGF-β1 的调节性 γδ T 细胞的驻留和极化。
DOI：
10.1038/s41419-019-1380-0
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发表时间：
2019-02-08
影响因子：
9
通讯作者：
Li, Ming-Qing
中科院分区：
文献类型：
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作者：
Chang, Rui-Qi;Shao, Jun;Li, Ming-Qing
蜕膜γ-增量T细胞在妊娠成功过程中起着重要的作用，然而，蜕膜中的γ-增量T细胞的定位和极化尚不清楚。在本研究中，我们观察到正常妊娠蜕膜基质细胞(DSCs)上核因子-kappa B受体激活剂B配体(RANKL)及其受体在d-Gamma-Delta T细胞上的排名高于复发性自然流产(RSA)患者。DSCs表达的RANKL可诱导外周血γ-βT细胞极化为Foxp3+-γ-βT细胞，并上调转化生长因子-β1的表达。这一过程是通过激活核因子-kappa-轻链活化B细胞(NF-kappa B)来实现的。此外，RANKL在体外可促进d-Gamma-Delta T细胞与DSCs的黏附，这与上调DSC表面ICAM-1和VCAM-1以及上调d-Gamma-Delta T细胞上的整合素有关。RANKL基因敲除导致子宫总数减少。细胞、Foxp3+γ-T细胞和转化生长因子-β1的表达，并增加小鼠的妊娠丢失。这些结果表明，RANKL是母胎耐受的关键调节因子，在妊娠早期通过触发产生转化生长因子-β1的Foxp3+γ-Delta T细胞的极化和滞留而发挥作用。RANKL/RANK的异常低水平导致DSCs与d-Gamma-Delta T细胞之间的对话障碍，从而导致妊娠丢失。这一观察结果为检测潜在的标记物以预警妊娠丢失提供了科学依据。
Decidual gamma delta T (d gamma delta T) cells play an essential role during successful pregnancy; however, the residence and polarization of gamma delta T cells in decidua remain unclear. In this study, we observed higher levels of receptor activator for nuclear factor-kappa B ligand (RANKL) on decidual stromal cells (DSCs), and its receptor RANK on d gamma delta T cells in decidua from normal pregnancy compared with patients with recurrent spontaneous abortion (RSA). RANKL expressed by DSCs can induce the polarization of peripheral blood gamma delta T (p gamma delta T) and d gamma delta T cells to Foxp3 + gamma delta T cells, and upregulate the expression of transforming growth factor (TGF)-beta 1. This process is mediated through activation of nuclear factor kappa-light-chainenhancer of activated B cells (NF-kappa B). In addition, RANKL promotes the adhesion of d gamma delta T cells to DSCs in vitro, which is associated with the upregulation of ICAM-1 and VCAM-1 on DSCs and integrins on d gamma delta T cells. RANKL knockout leads to the decreased numbers of uterus total.d. cells, Foxp3+gamma delta T cells and the expression of TGF-beta 1, and the increased pregnancy loss in mice. These results suggest that RANKL is a pivotal regulator of maternal-fetal tolerance by triggering the polarization and residence of TGF-beta 1-producing Foxp3+gamma delta T cells in early pregnancy. The abnormal low level of RANKL/RANK results in pregnancy loss because of the dialogue disorder between DSCs and d gamma delta T cells. This observation provides a scientific basis on which a potential marker can be detected to early warning of pregnancy loss.