CXCL12 enhances exogenous CD4+CD25+ T cell migration and prevents embryo loss in non-obese diabetic mice

CXCL12 enhances exogenous CD4+CD25+ T cell migration and prevents embryo loss in non-obese diabetic mice
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DOI:
10.1016/j.fertnstert.2008.01.109
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发表时间:
2009-06-01
影响因子:
6.7
通讯作者:
Lin, Qi-de
Lin, Qi-de
中科院分区:
医学2区
文献类型:
--
作者:
Lin, Yi;Xu, Liang;Lin, Qi-de

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目的:为了研究CXCL 12在调节性T(Treg)细胞迁移中的可能作用。设计:基于动物模型的研究。设置:学术。动物:将妊娠非肥胖糖尿病(NOD)小鼠与非免疫缺陷小鼠进行比较。干预:体内和体外CXCL 12诱导。主要结果测量:流式细胞术分析和Treg细胞迁移测定。结果:在同基因和异基因妊娠NOD小鼠中观察到显著高百分比的自发胚胎吸收。通过Treg细胞和CXCL 12注射治疗,异基因妊娠NOD小鼠中的胚胎丢失百分比显著降低;然而,在同基因妊娠NOD小鼠中未观察到这种效果。此外,通过体外和体内迁移测定证实了CXCL 12诱导的Treg细胞的迁移。CXCL 12的特异性受体CXCR 4在Treg细胞上的表达高于非Treg CD 3(+)T细胞,而CXCL 12在妊娠早期主要表达于细胞角蛋白7(+)滋养层细胞,在妊娠期间表达逐渐下降。CXCL 12可以使CXCR 4(+)Treg细胞迁移到妊娠子宫中,为胎儿建立有益的微环境。(Fertil Steril(R)2009;91:2687-96.(C)2009年由美国生殖医学协会。
Objective: To investigate the possible role of CXCL12 in the migration of regulatory T (Treg) cells.Design: Animal model-based study.Setting: Academic.Animal(s): Pregnant non-obese diabetic (NOD) mice were compared with non-immunodeficient mice.Intervention(s): In vivo and in vitro CXCL 12 induction.Main Outcome Measure(s): Flow cytometric analysis and Treg cell migratory assay.Result(s): A significantly high percentage of spontaneous embryo resorption was observed in both syngeneic and allogeneic pregnant NOD mice. The percentage of embryo loss in allogeneic pregnant NOD mice was significantly decreased by treatment with Treg cells and CXCL12 injection; however, no such effect was observed in syngeneic pregnant NOD mice. In addition, the migration of Treg cells induced by CXCL12 was confirmed by both in vitro and in vivo migratory assays. CXCR4, the specific receptor for CXCL12, was expressed more intensively on Treg cells than on non-Treg CD3(+) T cells, whereas CXCL12 was dominantly expressed in cytokeratin 7(+) trophoblast cells at an early stage of gestation, and its expression reduced gradually during pregnancy.Conclusion(s): The higher level of embryo loss in allogeneic pregnant NOD mice may be due to the lack of Treg cells. CXCL12 can cause CXCR4(+) Treg cells to migrate into the pregnant uterus and establish a beneficial micro-environment for the fetus. (Fertil Steril (R) 2009;91:2687-96. (C)2009 by American Society for Reproductive Medicine.)