A pivotal role for galectin-1 in fetomaternal tolerance
A pivotal role for galectin-1 in fetomaternal tolerance
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DOI：
10.1038/nm1680
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发表时间：
2007-12-01
期刊：
影响因子：
82.9
通讯作者：
Arck, Petra C.
中科院分区：
文献类型：
--
作者：
Blois, Sandra M.;Ilarregui, Juan M.;Arck, Petra C.
成功的妊娠需要母体免疫-内分泌机制同步适应胎儿。在这里，我们表明，半乳糖凝集素-1（Gal-1），一种免疫调节聚糖结合蛋白，具有关键作用，赋予母胎耐受性。与妊娠失败期间Gal-1表达显著降低一致，Gal-1缺陷（Lgals 1（-/-））小鼠在异基因交配中显示出比野生型小鼠更高的胎儿丢失率，而在同基因交配中胎儿存活率不受影响。重组Gal-1治疗通过多种机制防止胎儿丢失并恢复耐受性，包括诱导致耐受性树突状细胞，这反过来又促进了体内分泌白细胞介素-10（IL-10）的调节性T细胞的扩增。因此，Gal-1的保护作用在缺乏调节性T细胞或缺乏IL-10的小鼠中被废除。此外，我们提供的证据Gal-1和孕酮之间的协同作用，在维持妊娠。因此，Gal-1是母胎耐受的关键调节因子，在先兆妊娠中具有潜在的治疗意义。
A successful pregnancy requires synchronized adaptation of maternal immune-endocrine mechanisms to the fetus. Here we show that galectin-1 (Gal-1), an immunoregulatory glycan-binding protein, has a pivotal role in conferring fetomaternal tolerance. Consistently with a marked decrease in Gal-1 expression during failing pregnancies, Gal-1-deficient (Lgals1(-/-)) mice showed higher rates of fetal loss compared to wild-type mice in allogeneic matings, whereas fetal survival was unaffected in syngeneic matings. Treatment with recombinant Gal-1 prevented fetal loss and restored tolerance through multiple mechanisms, including the induction of tolerogenic dendritic cells, which in turn promoted the expansion of interleukin-10 (IL-10)-secreting regulatory T cells in vivo. Accordingly, Gal-1's protective effects were abrogated in mice depleted of regulatory T cells or deficient in IL-10. In addition, we provide evidence for synergy between Gal-1 and progesterone in the maintenance of pregnancy. Thus, Gal-1 is a pivotal regulator of fetomaternal tolerance that has potential therapeutic implications in threatened pregnancies.