Prevention of embryo loss in non-obese diabetic mice using adoptive ITGA2+ISG20+ natural killer-cell transfer

Prevention of embryo loss in non-obese diabetic mice using adoptive ITGA2+ISG20+ natural killer-cell transfer
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使用过继性 ITGA2 ISG20 自然杀伤细胞移植预防非肥胖糖尿病小鼠的胚胎丢失。

DOI:
10.1530/rep-08-0412
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发表时间:
2009-06-01
期刊:
影响因子:
3.8
通讯作者:
Li, Da-Jin
Li, Da-Jin
中科院分区:
生物学3区
文献类型:
--
作者:
Lin, Yi;Wang, Huiqi;Li, Da-Jin

文献摘要

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调节性T细胞和调节性自然杀伤(NK)细胞可能在维持妊娠中起关键作用。在本研究中,我们发现,在同种异体和同基因妊娠的非肥胖糖尿病(NOD)小鼠中均观察到自然流产的比例显著较高。通过给予抗去唾液酸神经节苷脂 - N - 四糖基神经酰胺以清除NK细胞,同种异体妊娠小鼠的胚胎丢失比例进一步增加,但通过从正常小鼠过继转移ITGA2(+)ISG20(+)(CD49b(+) CD25(+))NK细胞,该比例降低。在同基因妊娠的NOD小鼠中未观察到这种趋势。分析了NK细胞上CXCR4(CXCL12的特异性受体)的表达模式,并通过体外和体内迁移试验证实了NK细胞的迁移。由于先前已证实小鼠滋养层细胞产生CXCL12,我们的研究结果表明,外周表达CXCR4的ITGA2(+)ISG20(+) NK细胞向妊娠子宫的募集可能在调节母胎耐受中起重要作用。《生殖》(2009年)137卷,943 - 955页
Both regulatory T cells and regulatory natural killer (NK) cells may play essential roles in the maintenance of pregnancy. In this study, we show that a significantly high percentage of spontaneous embryo loss was observed in both allogeneic and syngeneic pregnant non-obese diabetic (NOD) mice. The percentage of embryo loss in allogeneic pregnant mice was further increased by the administration of anti-asialo ganglio-N-tetraosylceramide to deplete NK cells, but was decreased by the adoptive transfer of ITGA2(+)ISG20(+) (CD49b(+) CD25(+)) NK cells from normal mice. No such trend was observed in syngeneic pregnant NOD mice. The pattern of CXCR4 (specific receptor for CXCL12) expression on NK cells was analyzed and NK-cell migration was confirmed by in vitro and in vivo migratory assays. Since CXCL12 production by murine trophoblast cells was confirmed previously, our findings suggest that the recruitment of peripheral CXCR4-expressing ITGA2(+)ISG20(+) NK cells into pregnant uteri may be important in the regulation of feto-maternal tolerance. Reproduction (2009) 137 943-955