脂生物合成对于TH17细胞分化过程中的代谢重新连接至关重要
Thiruvaimozhi Abimannan1, Velayoudame Parthibane1, Si-Hung Le2
1Cancer and Developmental Biology Laboratory, National Cancer Institute, Frederick, MD, USA.
Science advances
|April 24, 2024
概括
脂对T助手17细胞发育至关重要. 抑制它们的合成可以通过减少炎症和代谢功能障碍来保护自身免疫性疾病.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞的新陈代谢
- 生物化学 生物化学
背景情况:
- 辅助T细胞17 (TH17) 细胞在自身免疫性疾病中起着关键作用.
- 代谢过程对TH17细胞的分化和功能至关重要.
研究的目的:
- 为了研究新兴脂合成在TH17细胞发育中的作用.
- 阐明将脂合成与TH17细胞代谢和功能联系起来的分子机制.
主要方法:
- 研究了SPTLC1缺乏对TH17细胞分化在体外和体内的影响.
- 评估了糖解,反应性氧物种 (ROS) 生产和关键信号通路 (mTORC1,HIF-1α,c-Myc).
- 评估了SPTLC1缺乏对实验性自身免疫脑膜炎和T细胞转移性结肠炎模型的影响.
主要成果:
- SPTLC1 缺陷影响了新的脂合成,导致TH17细胞的糖解减少.
- 这种损伤是由通过增强的NADPH氧化酶2活性增加的ROS介导的.
- 增加的ROS抑制了mTORC1的激活,并降低了HIF-1α和c-Myc诱导的甘油性基因的表达.
- 在实验小鼠中,SPTLC1 缺乏提供了对自身免疫性脑膜炎和大肠炎的保护.
结论:
- 新的脂生物合成途径对于TH17细胞的发育和功能至关重要.
- 准这种途径对自身免疫性疾病具有治疗潜力.
- 甲状腺脂质代谢极大地影响了自适应性免疫反应.
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