孕产妇的炎症调节胎儿的急性骨髓形成
Amélie Collins1, James W Swann2, Melissa A Proven2
1Columbia Stem Cell Initiative, Columbia University Irving Medical Center, New York, NY 10032, USA; Division of Neonatology-Perinatology, Department of Pediatrics, Columbia University Irving Medical Center, New York, NY 10032, USA.
Cell
|March 1, 2024
概括
新生儿容易受到感染. 像IL-10这样的母体抗炎因素会阻止胎儿的干细胞产生免疫反应,从而增加怀孕期间的感染风险.
科学领域:
- 免疫学
- 发育生物学
- 血液形成
背景情况:
- 新生儿对炎症和感染的易感性增加.
- 胎儿造血干细胞和前代细胞 (HSPC) 对免疫发育至关重要,但它们对炎症信号的反应尚未完全理解.
- 在新生儿中,低中性粒细胞数增加了感染的风险.
研究的目的:
- 为了研究晚期胎儿肝脏 (FL) 鼠 HSPC 对炎症的反应.
- 测试突发骨髓形成障碍导致围产期中性衰竭的假设.
- 确定影响胎儿对炎症反应的母体因素.
主要方法:
- 对胎儿肝脏 (FL) 小鼠的造血干细胞和原始细胞 (HSPC) 的分析.
- 在胎儿的HSPC中评估骨髓细胞的产生和转录程序.
- 用炎症刺激激发胎儿的HSPC.
- 对孕产妇的抗炎因素,特别是IL-10的研究.
- 评估胎儿HSPC激活和生存的母性IL-10淘汰小鼠模型.
主要成果:
- 胎儿的HSPC在稳定状态下表现出有限的骨髓细胞产生,并且不激活像成年人一样的EM转录程序.
- 胎儿的HSPC可以在体外对诱导EM的刺激做出反应.
- 孕产妇的IL-10限制了胎儿在子宫内对EM通路的HSPC激活.
- 母体IL-10的损失会恢复胎儿HSPC中的EM激活,但会导致胎儿死亡.
结论:
- 母体的抗炎反应,主要是IL-10,通过抑制胎儿的EM通路来维持妊娠.
- 这种抑制使胎儿的HSPC对感染信号无反应,增加了新生儿的敏感性.
- 在维持怀孕和胎儿免疫反应之间存在进化上的权衡.
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