中性粒细胞的衰老是由微生物组调节的
Dachuan Zhang1,2, Grace Chen1,2, Deepa Manwani3
1Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Nature
|September 17, 2015
概括
微生物群驱动中性粒细胞衰老, 形成一个过度活跃的亚群, 消耗肠道微生物显著降低了老化的中性粒细胞,改善了状细胞疾病和败血症模型中的疾病结果和器官损伤.
科学领域:
- 免疫学
- 微生物学
- 血液学
背景情况:
- 中性粒细胞是关键的免疫细胞,但可以在炎症中引起组织损伤.
- 证据表明中性粒细胞不是一个同质的群体,异质性可能来自老化.
- 老化的中性粒细胞表现出不同的特征,包括CXCR4上调和L-选择蛋白表达的减少.
研究的目的:
- 在体内研究中性细胞衰老的作用.
- 在炎症期间确定老化的中性粒细胞的功能性质.
- 确定调节中性粒细胞衰老的因素及其对疾病的影响.
主要方法:
- 在老鼠模型中进行体内衰老分析.
- 评估中性粒细胞激活标志物 (例如αMβ2整体素) 和中性粒细胞外陷 (NET) 的形成.
- 在状细胞疾病和败血性休克模型中,微生物群枯竭策略和疾病发病的评估.
主要成果:
- 在体内,中性粒细胞的促炎活性随着循环年龄的增长而增加.
- 老化的中性粒细胞表现出增强的αMβ2整合素激活和NET形成.
- 微生物群通过托尔类受体和骨髓分化因子88信号驱动中性粒细胞的衰老.
- 微生物群的枯竭减少了老化的中性粒细胞,改善了疾病的结果.
结论:
- 中性粒细胞在循环中的老化增强了促炎功能.
- 肠道微生物群在促进疾病的老化中性粒细胞子组中起着至关重要的作用.
- 向微生物群可能是缓解中性粒细胞驱动的炎症和器官损伤的治疗策略.
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