组织内存T细胞的存活需要外源性脂质吸收和代谢
Youdong Pan1, Tian Tian1, Chang Ook Park1
1Department of Dermatology and Harvard Skin Disease Research Center, Brigham and Women's Hospital, Boston, Harvard Medical School, Boston, Massachusetts, USA.
Nature
|February 21, 2017
概括
组织内存T (TRM) 细胞使用脂肪酸结合蛋白4和5 (FABP4/5) 来吸收自由脂肪酸,为其线粒体代谢提供长期生存和病原体保护. 这突出了TRM细胞持久性和功能的新途径.
科学领域:
- 免疫学
- 细胞生物学
- 代谢过程
背景情况:
- 组织内存T (TRM) 细胞对于屏障部位的长期免疫是至关重要的.
- 支持TRM细胞长寿的代谢途径在很大程度上是未知的.
研究的目的:
- 阐明CD8+TRM细胞持续存活的分子机制.
- 研究脂质代谢在TRM细胞功能和持久性的作用.
主要方法:
- 在小鼠CD8+TRM细胞中基因表达的分析.
- 产生和评估T细胞特异性的Fabp4/Fabp5淘汰小鼠.
- 在体外和体内测试测量自由脂肪酸吸收,线粒体代谢和细胞存活率.
- 病毒挑战模型来评估保护性免疫力.
主要成果:
- 小鼠CD8+TRM细胞高度表达FABP4和FABP5,促进自由脂肪酸 (FFA) 的吸收.
- 特定于T细胞的FABP4/5缺乏会损害FFA的吸收,降低T细胞的存活率,并降低氧化代谢.
- 抑制线粒体FFAβ氧化会影响TRM细胞的持久性和保护性免疫力.
- 人类TRM细胞也显示FABP4/5表达的增加和FFA吸收的增加.
结论:
- FABP4和FABP5对于CD8+TRM细胞的维护,寿命和保护功能至关重要.
- CD8+TRM细胞利用外源性FFAs和线粒体的氧化代谢进行组织持久性.
- 向FFA代谢是一种增强TRM细胞介导免疫力的潜在策略.
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