母亲的IL-10限制了胎儿的紧急骨髓形成
bioRxiv : the preprint server for biology
|September 25, 2023
概括
孕产妇的互白素-10 (IL-10) 阻止胎儿的造血干细胞和前代细胞 (HSPCs) 激活紧急骨髓形成,导致新生儿的中性贫血. 这种母亲的抗炎反应损害了胎儿的感染防御能力.
科学领域:
- 免疫学 免疫学 免疫学
- 发展生物学 发展生物学
- 血液形成 血液形成 血液形成
背景情况:
- 与成年人相比,新生儿对炎症和感染的易感性增加.
- 胎儿造血干细胞和原生细胞 (HSPCs) 对于免疫发育至关重要,但它们对炎症的反应尚未完全理解.
研究的目的:
- 调查晚期胎儿肝 (FL) 鼠 HSPC 如何对炎症作出反应.
- 测试假设,胎儿HSPCs中的紧急骨髓形成 (EM) 损伤有助于围产期中性衰竭.
主要方法:
- 对胎儿和成年HSPC对炎症刺激的分子反应进行比较.
- 评估了母亲因子,特别是IL-10在调节胎儿HSPC激活中的作用.
- 使用了具有改变母体IL-10水平的小鼠模型.
主要成果:
- 胎儿的HSPCs显示出有限的稳定状态髓状细胞生产,并且无法激活经典的EM转录程序.
- 胎儿的HSPCs可以对*in vitro*诱导的EM刺激做出反应,但被*in utero*由母体IL-10抑制.
- 失去母体IL-10恢复了胎儿HSPC中的EM激活,但导致过早分娩.
结论:
- 母亲的IL-10限制胎儿的HSPCs参与EM通路,影响髓状细胞输出.
- 这种限制可能解释了在败血症新生儿中观察到的中性.
- 通过母亲的抗炎因素维持怀孕和胎儿的免疫反应之间存在进化上的权衡.
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