鱼类使用CTLA-4免疫检查点来抑制mTORC1-控制的T细胞糖解和免疫力
Jiansong Zhang1, Xiumei Wei1, Qian Zhang1
1State Key Laboratory of Estuarine and Coastal Research, School of Life Sciences, East China Normal University, Shanghai, China.
Journal of immunology (Baltimore, Md. : 1950)
|February 16, 2024
概括
蒂拉皮亚的细胞毒性T淋巴细胞相关蛋白4 (CTLA-4) 通过抑制mTORC1 / c-Myc控制的糖解抑制T细胞反应,揭示了早期脊椎动物的免疫检查点功能.
科学领域:
- 免疫学 免疫学 免疫学
- 比較免疫學 比較免疫學
- 鱼类免疫学 鱼类免疫学
背景情况:
- 细胞毒性T-淋巴细胞相关蛋白4 (CTLA-4) 是一个关键的免疫检查点,调节哺乳动物的T细胞反应.
- 在早期脊椎动物 (如骨鱼) 中,CTLA-4的功能和机制在很大程度上仍未被探索.
研究的目的:
- 研究CTLA-4在尼罗河鱼 (Oreochromis niloticus) 的T细胞反应中的作用和调节机制.
- 阐明CTLA-4如何影响T细胞激活,增殖,亡和骨鱼的细胞毒性.
主要方法:
- 研究了CTLA-4表达在皮淋巴细胞组织和淋巴细胞中.
- 在Edwardsiella piscicida感染期间在体外和体内利用CTLA-4阻断.
- 分析了T细胞激活,增殖,亡和细胞毒性.
- 研究了鱼CTLA-4与CD28和B7.2/CD86.2的相互作用.
- 评估了抑制mTORC1信号传递,c-Myc和糖解对CTLA-4阻塞效应的影响.
主要成果:
- 鱼CTLA-4表达在刺激和感染时被上调.
- CTLA-4阻塞增强了T细胞激活,增殖和细胞毒性,同时减少了细胞亡.
- 提拉皮亚CTLA-4通过与B7.2/CD86.2结合来对抗CD28介导的辅助刺激.
- CTLA-4通过抑制mTORC1/c-Myc驱动的糖解来抑制T细胞反应.
结论:
- 在尼罗河鱼中,CTLA-4负面调节T细胞激活和效应器功能.
- 早期的脊椎动物拥有复杂的机制,包括免疫检查点和代谢重编程,以维持免疫恒常.
- 通过代谢控制抑制T细胞免疫力的CTLA-4的作用在脊椎动物中保持不变.
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