通过Mevalonate途径诱导受训免疫的代谢
Siroon Bekkering1, Rob J W Arts2, Boris Novakovic3
1Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands; Department of Experimental Vascular Medicine, Academic Medical Centre, Amsterdam, the Netherlands.
Cell
|January 13, 2018
概括
通过激活关键信号通路,诱导骨髓细胞中的训练免疫力. 类药物阻断了这一过程,而HIDS患者的甲基酸积累导致了训练的免疫表型.
科学领域:
- 免疫学
- 代谢过程
- 表观遗传学
背景情况:
- 在微生物刺激后,先天免疫细胞表现出记忆,称为训练免疫.
- 代谢途径越来越多地被认为是免疫细胞功能和记忆中的作用.
研究的目的:
- 研究代谢信号在诱导训练免疫的作用.
- 确定参与训练免疫的特定代谢物和途径.
主要方法:
- 对胆固醇合成途径的药理和遗传操纵.
- 分析氨酸水平及其对免疫细胞的下游影响.
- 在预防训练免疫力方面研究他的有效性.
- 从患有高免疫球蛋白D综合征 (HIDS) 的患者中检查单细胞.
主要成果:
- 激活胆固醇合成途径,特别是氨酸的产生,对于骨髓细胞的训练至关重要.
- 通过IGF1-R和mTOR激活进行培训,导致表观遗传修饰.
- 类他类药物抑制甲基酸盐的产生,并防止训练免疫诱导.
- 患有甲基酸酶缺乏症的HIDS患者表现出构成性训练免疫力.
结论:
- 梅瓦诺酸是培养免疫力的关键代谢媒介.
- 这一发现阐明了HIDS的病理生理学,并建议对过度活跃的训练免疫的疾病进行治疗.
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