饮食中的多不和脂肪酸通过Nrf2-依赖控制铁灭症来调节树突细胞功能
Deepika Awasthi1,2, Erin K McMinn1, Camilla Salvagno1,2
1Department of Obstetrics and Gynecology, Weill Cornell Medicine. New York, NY 10065, USA.
Research square
|December 3, 2025
概括
饮食中的多不和脂肪酸 (PUFA) 通过调节铁亡,影响树突细胞 (DC) 功能. 欧米茄-3 PUFA 增强了 DC 活性和抗癌免疫力,而欧米茄-6 PUFA 降低了免疫力.
科学领域:
- 免疫学 免疫学 免疫学
- 代谢途径 代谢途径
- 癌症研究 癌症研究
背景情况:
- 树突细胞 (DCs) 对于适应性免疫非常重要.
- 饮食脂质对DC代谢和功能的影响尚不清楚.
- 脂质代谢显著影响免疫细胞功能.
研究的目的:
- 研究饮食中的多不和脂肪酸 (PUFA) 如何影响树突细胞 (DC) 的新陈代谢和功能.
- 探索Nrf2-ferroptosis通路在调解这些效应中的作用.
- 确定饮食中PUFAs在癌症免疫治疗中的治疗潜力.
主要方法:
- 用n-3或n-6PUFAs丰富的饮食养小鼠.
- 评估DC功能,包括抗原呈现和T细胞原始化.
- 测量氧化应激的标志物,谷氨水平和铁.
- 使用药理上的Nrf2激活和铁灭抑制.
- 在转移性卵巢癌模型中评估采用DCs的采用免疫疗法的疗效.
主要成果:
- 富含n-6PUFA的饮食抑制了DC Nrf2信号传递,减少了谷氨,并诱导了铁亡,损害了抗原呈现.
- 饮食中的n-3PUFA增强了Nrf2信号传递和还原平衡,保持了DC功能和T细胞原始化.
- 在被食n-6PUFA的小鼠中,药理Nrf2激活或ferroptosis抑制挽救了DC功能.
- 使用n-3PUFA受条件的DCs的采用免疫疗法证明了对转移性卵巢癌的持久,T细胞依赖的控制.
结论:
- 饮食中的PUFA是DCs中Nrf2-glutathione-ferroptosis轴的关键调节者.
- 这条路径代表了一个对氧化还原敏感的代谢检查点,影响DC功能.
- 通过饮食中的PUFA调节DC代谢可以提高癌症免疫治疗的疗效.
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