亡释放硫化以抑制Th17细胞分化
Qianmin Ou1, Xinhua Qiao2, Zhengshi Li1
1South China Center of Craniofacial Stem Cell Research, Hospital of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510080, China.
Cell metabolism
|December 19, 2023
概括
亡调节硫化 (H2S) 的产生,这对免疫恒温至关重要. 这项研究揭示了由亡细胞产生的H2S会影响T辅助17 (Th17) 细胞的分化.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 细胞亡对于免疫常态稳定至关重要,在人类中,每天有超过500亿个细胞经历着编程细胞死亡.
- 硫化 (H2S) 在免疫反应功能中起着至关重要的作用.
- 亡和H2S产生之间的调节关系仍然不清楚.
研究的目的:
- 调查细胞亡是否调节H2S的产生.
- 阐明H2S在Th17细胞分化中的作用.
- 确定连接H2S,细胞亡和免疫细胞调节的分子机制.
主要方法:
- 在亡缺陷的MRL/lpr和Bim-/-小鼠中分析H2S水平.
- 在体内对Th17细胞分化的评估和使用H2S补充的救援实验.
- 检测H2S产生的酶在apoptotic细胞和囊泡 (apoVs).
- 研究H2S介导的蛋白F (Sep15) 的翻译后修饰 (硫化) 以及其对STAT1/STAT3酸化的影响.
主要成果:
- 缺失亡的小鼠表现出显著降低的H2S水平和异常的Th17细胞分化,这些都是通过H2S恢复的.
- 鉴定出亡细胞和囊泡是H2S的重要来源.
- 显示H2S在氨酸38 (Sep15C38) 中硫化Sep15,促进STAT1酸化和抑制STAT3酸化,从而抑制Th17细胞分化.
结论:
- 亡是H2S恒温的关键调节者.
- 亡性新陈代谢是内源H2S的一个关键来源.
- H2S,通过Sep15硫化,在抑制Th17细胞分化方面发挥着独特的作用,突出了免疫调节中的新途径.
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