广谱抗生素破坏了同源的恒常性乙细胞分裂
Pedro H V Saavedra1,2, Alissa J Trzeciak3, Allie Lipshutz3
1Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA. p.saavedra@northeastern.edu.
肠道微生物通过黄酸盐影响了细胞清除,即死细胞的清除. 这一发现揭示了抗生素如何破坏免疫系统的平衡,并可能与炎症性疾病有关.
科学领域:
- 免疫学 免疫学 免疫学
- 微生物组研究 微生物组研究
- 细胞生物学 细胞生物学
背景情况:
- 细胞化或细胞化的细胞清除对于组织健康和预防自身免疫性疾病至关重要.
- 虽然已知局部信号调节了血细胞分裂,但远程信号的作用尚不清楚.
研究的目的:
- 为了研究远程信号,特别是来自肠道微生物群的信号,是否调节恒常性血细胞分裂.
- 阐明肠道微生物群代谢物对细胞发生影响的机制.
主要方法:
- 使用了肠道微生物群枯竭的小鼠模型 (抗生素,万科米辛,无细菌).
- 向巨细胞和小鼠注射黄酸盐,评估细胞的效率和能力.
- 在巨细胞上进行批量和单细胞RNA测序,以识别转录变化.
主要成果:
- 消耗的肠道微生物群导致大腹巨细胞 (LPMs) 中的细胞衰竭.
- 来自微生物群的酸盐直接增强了小鼠和人类巨细胞的细胞分裂.
- 丁酸盐挽救了抗生素诱导的细胞衰变缺陷,并提高了LPM中的细胞衰变受体TIM-4的调节.
- 在接受抗生素治疗的小鼠中,有缺陷的血球细胞分裂会使狼疾病的严重程度恶化.
结论:
- 恒常性乙细胞分裂取决于来自肠道微生物群的遥远代谢信号.
- 由于肠道失生症导致的缺陷性乙细胞分裂可能解释了抗生素使用与炎症状况之间的关联.
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