澳大利亚昆士兰大学余迪课题组近日取得一项新成果。经过不懈努力，他们揭示了脂质代谢驱动饮食对T细胞凋亡和免疫的影响。该研究于2026年3月4日发表于国际一流学术期刊《自然》杂志上。

本研究表明，在小鼠中，T细胞对铁腐病的抗性主要取决于标准啮齿动物饮食的组成，饮食对铁腐病（DEFs）的影响在调节T细胞稳态和免疫反应中起着至关重要的作用。DEFs与微生物群无关，由饮食中多不饱和脂肪酸和单不饱和脂肪酸（PUFAs和MUFAs）的变化驱动，这些变化导致淋巴组织和T细胞中脂质种类的丰度发生变化。

一致地，在多个健康队列中，人类T细胞对铁下垂的抵抗力也与血浆脂质谱相关，与主要脂质类别中的PUFA/MUFA比率呈负相关。在缺乏必需的脂质过氧化物清除剂GPX4的情况下，DEFs决定T细胞的恢复能力，并广泛调节T细胞依赖的体液免疫和T细胞介导的抗肿瘤免疫，包括在嵌合抗原受体T细胞治疗中。从机制上讲，ACSL4优先生物合成含PUFA的磷脂，在T细胞中高表达，并支持DEF介导的卵泡辅助T（T_FH）细胞生成和功能的调节。他们的发现揭示了脂质代谢在免疫中驱动DEFs的生理意义，并提出了针对脂质代谢的策略，以提高疫苗效力和T细胞介导的免疫治疗。

研究人员表示，铁凋亡是一种非凋亡性程序性细胞死亡的主要机制，它对外周血CD4⁺和CD8⁺ T细胞的稳态和功能起着关键的调节作用。

附：英文原文

Title: Lipid metabolism drives dietary effects on T cell ferroptosis and immunity

Author: Wang, Naiqi, Chen, Zhian, Yao, Yin, Sun, Chenglong, Wei, Wei, Sun, Lei, Zhang, Hao, Li, Feng, Butcher, Daniel, Sun, Shi-Ran, Gong, Jialei, Jiang, Yingxin Celia, Qi, Yanfei, Huang, Jingxuan, Nettelfield, Sam, Liu, Rui, Zheng, Xiaoyue, Li, Chenyu, Fu, Yang, Geng, Haoyuan, Zhao, Limin, Sun, Hongjian, Yang, Yang, Ge, Yexin, Pazhouhandeh, Mehrdad, Barlow, Christopher K., Jeppe, Katherine Joanna, Yunis, Joseph, Zhu, Chen, Wei, Yunbo, Liang, Xiaowen, Bridle, Kim, Frazer, David M., Tey, Siok-Keen, Li, Yuhua, Yang, Zhaohui, Shu, Minglei, Liu, Zheng, Crawford, Darrell, Yu, Di

Issue&Volume: 2026-03-04

Abstract: Ferroptosis, a major mechanism of non-apoptotic programmed cell death, critically regulates the homeostasis and functionality of peripheral CD4+ and CD8+ T cells1,2,3,4,5,6. Here we demonstrate that in mouse, resistance of T cells to ferroptosis depends critically on the composition of standard rodent diets, and that dietary effects on ferroptosis (DEFs) have a crucial role in regulation of T cell homeostasis and immune responses. DEFs are microbiota-independent and are driven by variations in dietary polyunsaturated and monounsaturated fatty acids (PUFAs and MUFAs) that lead to variations in abundance of lipid species in lymphoid tissues and T cells. Consistently, ferroptosis resistance of human T cells also correlated with plasma lipid profiles across multiple healthy cohorts, exhibiting negative associations with PUFA/MUFA ratios in major lipid classes. DEFs dictate T cell resilience in the absence of the essential lipid peroxide scavenger GPX4 and broadly modulate T cell-dependent humoral immunity and T cell-mediated anti-tumour immunity, including in chimeric antigen receptor T cell therapy. Mechanistically, ACSL4, which preferentially biosynthezises PUFA-containing phospholipids7, is highly expressed in T cells and underpins DEF-mediated regulation of follicular helper T (TFH) cell generation and function. Our findings reveal the physiological significance of lipid metabolism in driving DEFs in immunity and suggest strategies targeting lipid metabolism to enhance vaccine efficacy and T cell-mediated immunotherapy.

DOI: 10.1038/s41586-026-10193-4

Source: https://www.nature.com/articles/s41586-026-10193-4