由DAMP驱动的训练免疫:在严重疾病和慢性炎症中进行代谢和表观遗传重编程
Han G Kim1, Jaimar C Rincon1, Philip A Efron1
1Sepsis and Critical Illness Research Center, Department of Surgery, College of Medicine, University of Florida College of Medicine, Gainesville, FL, United States.
Frontiers in immunology
|December 10, 2025
概括
天生的免疫记忆或训练免疫 (TRIM) 涉及免疫细胞的代谢和表观遗传变化,它们对损伤相关的分子模式 (DAMPs) 作出反应. 这种重新连接会影响宿主防御在严重疾病,如败血症.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 代谢研究研究 代谢研究
背景情况:
- 天生的免疫记忆或训练免疫 (TRIM) 越来越多地被认为是其在宿主防御中的作用,与传统的适应性免疫观点形成鲜明对比.
- 天生免疫细胞如单细胞和巨细胞的代谢和表观遗传重编程是推动TRIM的关键机制.
- 与损伤相关的分子模式 (DAMPs) 是这些细胞变化的强有力的诱导因素.
研究的目的:
- 综合当前关于DAMP如何诱导训练免疫的免疫代谢重新连接和表观遗传修饰的知识.
- 探索这些机制在败血症,无菌炎症损伤和严重疾病中的作用.
- 识别知识缺口和调节先天免疫记忆的未来治疗点.
主要方法:
- 关于训练免疫,DAMP和免疫代谢的当前文献的综述.
- 对表观遗传机制 (例如,H3K4me1/H3K27ac) 和代谢转变 (例如,华堡效应) 的分析.
- 检查DAMPs在败血症,创伤和炎症性疾病中的作用.
主要成果:
- 像氧化LDL,HMGB1和线粒体DNA这样的DAMP通过mTOR/HIF-1α和SYK信号传递等途径触发免疫代谢重新连接.
- 表观遗传修饰和代谢转变定义了训练或容忍的免疫状态.
- 在危急疾病中持续暴露DAMP可以导致不适应性炎症或免疫抑制,影响长期免疫功能.
结论:
- 了解DAMP诱导的免疫代谢和表观遗传重编程对于理解训练免疫是至关重要的.
- 调节先天免疫记忆具有治疗潜力,可以改善重症患者的治疗结果.
- 需要对免疫耐受性的标准化TRIM模型,生物标志物和线粒体DAMP进行进一步的研究.
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