抗原受体刺激诱导了对致病性线粒体tRNA突变的净化选择
Jingdian Zhang1,2, Camilla Koolmeister1,2, Jinming Han3
1Department of Medical Biochemistry and Biophysics, and.
JCI insight
|September 8, 2023
概括
线粒体DNA (mtDNA) 突变会影响免疫细胞. 记忆T细胞和B细胞减少了致病性mtDNA,但突变仍然可以破坏免疫反应和T细胞功能.
科学领域:
- 免疫学 免疫学 免疫学
- 线粒体生物学 线粒体生物学
- 遗传学 是一个遗传学.
背景情况:
- 线粒体 (mt) tRNA基因突变会导致氧化酸化 (OXPHOS) 缺陷和多综合症状况.
- 线粒体疾病与免疫系统异常有关,但涉及异质性mtDNA突变的分子机制尚不清楚.
研究的目的:
- 调查异质体mtDNA突变如何在分子水平上影响免疫系统.
- 探索致病性mtDNA突变对T和B细胞种群及其功能的影响.
主要方法:
- 从小鼠和MELAS患者的T细胞,B细胞和髓状细胞中分析致病性mtDNA突变负担.
- 在增殖和代谢压力下对T和B细胞培养中的突变稀释的评估.
- 评估CD8+ T细胞代谢重塑和激活后的干扰素- (IFN-γ) 生产.
主要成果:
- 记忆T细胞和B细胞表现出较低的致病性mtDNA突变负载与天真细胞相比,即使在接种疫苗后.
- 病原性突变稀释在髓状细胞中不如淋巴状细胞显著.
- 抗原受体触发的增殖和代谢应激加速了T和B细胞培养中的C5024T突变稀释.
- 在C5024T突变失调CD8+ T细胞代谢重编程和IFN-γ的生产.
结论:
- 淋巴细胞的产生影响了线粒体DNA (mtDNA) 格局.
- 致病mtDNA变异可以调节免疫反应,特别是在记忆淋巴细胞.
- 了解这些机制对于管理具有免疫成分的线粒体疾病至关重要.
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