乳酸诱导转录抑制巨细胞的炎症反应通过基因素乙化
Weiwei Shi1, Tiffany J Cassmann1, Aditya Vijay Bhagwate2
1Department of Immunology, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA.
Cell reports
|February 8, 2024
概括
乳酸为巨细胞提供燃料,促进表观遗传变化,抑制炎症并诱导长期免疫耐受性. 这突出了乳酸.
科学领域:
- 免疫学 免疫学 免疫学
- 代谢过程中的代谢.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 乳酸是由肠道微生物群和宿主新陈代谢产生的,影响免疫细胞功能.
- 肠道微环境的乳酸生产对于组织平衡至关重要.
- 乳酸在调节巨细胞前炎性反应中的作用需要进一步研究.
研究的目的:
- 研究乳酸如何与细胞新陈代谢融合以影响巨细胞表观遗传学.
- 为了确定乳酸对巨细胞前炎性反应和基因表达的影响.
- 探索乳酸在诱导长期免疫抑制或耐受性方面的潜力.
主要方法:
- 对乳酸在巨细胞中的代谢作用的分析.
- 对表观遗传修饰的评估,特别是对基因组H3K27的乙化.
- 基因表达分析以确定关键的免疫抑制基因 (例如Nr4a1).
- 在乳酸预暴露后对脂聚糖的巨体反应的评估.
主要成果:
- 乳酸作为巨细胞的主要燃料来源,增强了素H3K27的乙化.
- 这种表观遗传修饰导致免疫抑制基因的表达,抑制促炎功能.
- 乳酸预暴露会诱导一种"训练有素的免疫抑制",从而导致对脂多糖的耐受性.
结论:
- 乳酸积极塑造巨细胞表观基因组,将它们转移到免疫抑制状态.
- 乳酸诱导的染色质重塑是建立宽容性组织微环境的关键机制.
- 这突显了一种涉及乳酸感应和巨细胞表观遗传调节的新型恒常路径.
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