CTRP9参与AdipoR1并促进T细胞糖解和免疫力
Kunming Li1, Jiansong Zhang1,2, Kang Li1,2
1State Key Laboratory of Estuarine and Coastal Research, School of Life Sciences, East China Normal University, 200241, Shanghai, China.
EMBO reports
|November 17, 2025
概括
阿迪波尼克丁受体 (AdipoR) 对T细胞有多种作用. 新的研究表明,CTRP9通过促进葡萄糖分解来增强T细胞免疫力,与抑制它的ADPN不同,这表明连接体选择性决定了AdipoR1的结果.
科学领域:
- 免疫学 免疫学 免疫学
- 代谢途径 代谢途径
- 细胞信号传递 细胞信号传递
背景情况:
- 阿迪波尼丁 (ADPN) 受体 (AdipoR) 在T细胞反应中发挥作用,但其信号效应有争议,可能促进或抑制T细胞功能.
- 虽然ADPN结合抑制T细胞反应,但多个AdipoR配体的存在表明配体多样性可能解释了这些差异效应.
研究的目的:
- 为了研究结合体多样性是T细胞免疫上AdipoR信号传递的差异效应的基础的假设.
- 阐明CTRP9和ADPN调节T细胞代谢和功能的独特机制.
主要方法:
- 利用鱼和小鼠模型研究AdipoR1与不同带的相互作用.
- 研究了由CTRP9-AdipoR1相互作用触发的信号级联,包括Ca2+流入和CaM-CaMKKβ-AMPK通路.
- 评估了CTRP9和ADPN对T细胞激活,增殖,新陈代谢 (糖解) 和CAR-T细胞体内抗瘤功效的影响.
主要成果:
- 在鱼中,替代性阿迪波金CTRP9与阿迪波R1接触,激活CaM-CaMKKβ-AMPK通路,并通过促进糖分解来增强T细胞激活,增殖和抗菌免疫力.
- 在小鼠中,CTRP9在促进T细胞激活,增殖和细胞因子产生方面发挥了保留作用.
- CTRP9提高了抗CD19CAR-T细胞对B细胞淋巴瘤的疗效,与ADPN对T细胞的抑制作用形成鲜明对比.
- 从机制上讲,CTRP9增强T细胞糖解,而ADPN则抑制了它.
结论:
- CTRP9在促进T细胞免疫力方面具有进化保守的作用,与ADPN的抑制作用不同.
- 对AdipoR1的连接体选择性是T细胞免疫结果的关键决定因素,影响T细胞代谢.
- CTRP9促进T细胞糖解,增强免疫反应,而ADPN抑制它.
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