肠道细菌的L-氨酸改变了新陈代谢和组织素甲基化,以驱动树突细胞耐受性
Qiang Tang1, Guangyue Fan1, Xianping Peng1
1Tianjin Institute of Immunology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), State Key Laboratory of Experimental Hematology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
Cell reports
|February 11, 2025
概括
肠道细菌代谢物L-lysine通过增强树突细胞 (DC) 中的血清素,甘氨酸和单碳代谢来促进免疫耐受性. 这种机制涉及组织素甲基化,在炎症期间恢复肠道平衡.
科学领域:
- 免疫学 免疫学 免疫学
- 微生物学 微生物学
- 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:
- 树突细胞 (DCs) 保持肠道对非有害抗原的免疫耐受性.
- 细菌代谢物诱导DC耐受性的精确机制尚未完全理解.
研究的目的:
- 为了阐明细菌代谢物诱导的免疫耐受性在DCs的机制.
- 确定L-氨酸在调节DC功能和肠道平衡中的作用.
主要方法:
- 研究了L-lysine对DCs中的血清素,甘氨酸,单碳 (SGOC) 代谢的影响.
- 使用的腺单酸盐 (AMP) 激活蛋白激酶 (AMPK) /乙辅酶A (AcCoA) - - 机理目标的拉巴胺素 (mTOR) 途径分析.
- 在特定基因促进体 (Tgfb, Stat3) 中评估了组分离子甲基化 (H3K79me2).
- 使用免疫炎症疾病和糖酸脱酶 (Phgdh) 条件淘汰的小鼠模型.
- 进行了单细胞RNA测序 (scRNA-seq) 分析.
主要成果:
- 细菌L-氨酸通过AMPK/mTOR轴激活DC中的SGOC代谢.
- 这种激活会增加S-adenosyl metionin (SAM) 和破坏端粒沉默1-like (DOT1L) 表达的破坏者.
- 在Tgfb和Stat3促销器中增强H3K79me2丰富促进DC免疫耐受性.
- 在炎症性疾病模型中,L-lysine通过诱导DC耐受性状态来恢复肠道平衡.
- 确定了负责L-lysine生产的细菌酶.
结论:
- 细菌L-氨酸是肠道免疫恒温的关键调节剂.
- 细菌L-lysine,SGOC新陈代谢和基因素甲基化之间的相互作用控制了DC耐受性.
- 这项研究揭示了一种由肠道共生细菌介导的免疫耐受性的新机制.
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