乳酸通过稳定树突细胞中的HIF-1α来限制中枢神经系统的自身免疫力
Liliana M Sanmarco1, Joseph M Rone1,2, Carolina M Polonio1
1Ann Romney Center for Neurologic Diseases, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA.
Nature
|August 9, 2023
概括
研究人员在树突细胞 (DC) 中发现了一种由乳酸驱动的反循环,该循环限制了自身免疫反应. 这一发现导致开发一种生产乳酸的益生菌来抑制T细胞自身免疫力.
科学领域:
- 免疫学
- 代谢途径
- 细胞生物学
背景情况:
- 树突细胞 (DCs) 参与自身免疫疾病的发病.
- 了解DC调节机制对于开发有针对性的疗法至关重要.
- 影响DC功能的遗传因素与自身免疫性疾病有关.
研究的目的:
- 确定控制自身免疫的直流功能的调节机制.
- 阐明免疫代谢在DC介导免疫反应中的作用.
- 开发针对T细胞自身免疫的新疗法.
主要方法:
- 单细胞和批量转录和代谢分析.
- 细胞特异性基因扰动研究.
- 一种乳酸产生益生菌的工程.
主要成果:
- 在涉及乳酸盐和NDUFA4L2的DC中确定了负反循环.
- 乳酸通过低氧诱导因子1α (HIF-1α) 上调NDUFA4L2.
- NDUFA4L2限制了线粒体的活性氧物种,抑制了致病性T细胞的激活.
结论:
- 确定了一种调节DC功能和限制自身免疫病理的免疫代谢途径.
- 一种合成的益生菌可以抑制T细胞自身免疫力.
- 这项研究为自身免疫性疾病提供了一种新的治疗方法.
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