Miscarriage induced by adoptive transfer of dendritic cells and invariant natural killer T cells into mice
Miscarriage induced by adoptive transfer of dendritic cells and invariant natural killer T cells into mice
复制标题
DOI：
10.1002/eji.201747162
复制
发表时间：
2018-06-01
影响因子：
5.4
通讯作者：
Takahashi, Hidemi
中科院分区：
文献类型：
--
作者：
Negishi, Yasuyuki;Ichikawa, Tomoko;Takahashi, Hidemi
意外胎儿丢失是妊娠的常见并发症之一；然而，许多流产的发病机制，特别是那些与感染无关的流产，是未知的。我们之前发现，当腹腔注射-半乳糖神经酰胺（-GalCer）诱导流产时，活化的DEC-205（+）树突状细胞（dc）和NK1.1（+）不变性自然杀伤T （iNKT）细胞被招募到小鼠的肌层。在这里，我们证明了decc -205（+）骨髓来源的dc与-GalCer共培养（decc -205(+) BMDCs-c/w -GalCer）的过继性转移直接诱导了同基因妊娠C57BL/6 （B6）小鼠和异体小鼠(B6 （f) x BALB/c (o)）的明显胎儿丢失，并伴随着肌层中活化iNKT细胞的积累。此外，从B6小鼠获得的NK1.1(+) iNKT细胞注射- galcer后，过继性转移促进了同基因J18((-/-)) （iNKT细胞缺陷）小鼠的流产。这些结果表明，decc -205(+) dc和NK1.1(+) iNKT细胞在糖脂抗原刺激和无菌炎症引起的胎儿丢失的起始过程中起着至关重要的作用。
Unexpected fetal loss is one of the common complications of pregnancy; however, the pathogenesis of many miscarriages, particularly those not associated with infections, is unknown. We previously found that activated DEC-205(+) dendritic cells (DCs) and NK1.1(+) invariant natural killer T (iNKT) cells are recruited into the myometrium of mice when miscarriage is induced by the intraperitoneal administration of -galactosylceramide (-GalCer). Here we demonstrate that the adoptive transfer of DEC-205(+) bone marrow-derived DCs cocultured with -GalCer (DEC-205(+) BMDCs-c/w--GalCer) directly induced marked fetal loss by syngeneic pregnant C57BL/6 (B6) mice and allogeneic mice (B6 (f) x BALB/c (o)), which was accompanied by the accumulation of activated iNKT cells in the myometrium. Further, the adoptive transfer of NK1.1(+) iNKT cells obtained from B6 mice injected with -GalCer facilitated miscarriages in syngeneic J18((-/-)) (iNKT cell-deficient) mice. These results suggest that DEC-205(+) DCs and NK1.1(+) iNKT cells play crucial roles required for the initiation of fetal loss associated with stimulation by glycolipid antigens and sterile inflammation.