撰文丨王聪 编辑丨王多鱼 排版丨水成文 2 型固有淋巴细胞 （ILC2） 在维持和保护屏障组织功能中发挥关键作用，但同时也驱动与代谢活动改变相 关的慢性炎症过程。识别并靶向驱动 ILC2 介导炎症的代谢通路，可能有助于恢复组织稳态。 2025 年 12 月 10 日，波恩大学医院的研究人员在 Cell 子刊 Immunity 上发表了题为： Tolerance to ferroptosis facilitates lipid metabolism and pathogenic type 2 immunity in allergic airway inflammation 的研究论文。 该研究发现， 对 铁死亡 的耐受性促进了 过敏性气道炎症 中的脂质代谢和致病性 2 型免疫，表明了 对于 抗氧化系统依赖性的增强，代表了一种代谢脆弱性，可作为 哮喘 的潜在治疗靶点。 在这项新研究中，研究团队发现，在 过敏性气道炎症 中，致病性 ILC2 依赖 胱氨酸 来增强代谢适应性并 维持生存。 胱氨酸的摄取促进 谷胱甘肽 （GSH） 的合成，该过程与谷胱甘肽过氧化物酶-4 （GPX4） 和硫氧还蛋白 还原酶-1 （TXNR ...

Core Viewpoint - The study reveals a mechanism of liver-breast metabolic communication that drives cancer progression, particularly highlighting the role of exosomes derived from non-alcoholic fatty liver disease (NAFLD) in promoting breast cancer development [9]. Group 1: Research Findings - Exosomes from fatty liver induce the release of free fatty acids in breast adipocytes, thereby promoting breast cancer progression [3][10]. - The study establishes a correlation between NAFLD and increased breast cancer risk in atypical hyperplasia individuals, as well as poor prognosis in breast cancer patients [4]. - The accumulation of fatty liver-derived exosomes in adipocytes contributes to the formation of a pro-tumor microenvironment in the breast [4]. Group 2: Mechanisms Involved - The targeting of adipocytes by exosomes is mediated by the interaction between ErbB4 and Nrg4 [4][10]. - TRMT10C in the exosomes is transferred to mitochondria, leading to m1A modification of mitochondrial mRNA, which suppresses the translation of ND5 and ND6, resulting in increased reactive oxygen species (ROS) levels and accelerated tumor progression [4][10]. Group 3: Prognostic Indicators - Plasma ErbB4-positive exosomes are identified as an independent prognostic indicator for breast cancer patients with NAFLD [5].

Core Viewpoint - Ferroptosis is a newly discovered iron-dependent form of programmed cell death that plays a significant role in the development of various diseases, including cancer [2][4]. Group 1: Mechanism of Ferroptosis - Reactive oxygen species (ROS) are crucial in initiating lipid peroxidation and ferroptosis, significantly affecting chemotherapy resistance in cancer [3][10]. - The study published in Nature Cell Biology reveals that O-GlcNAc transferase (OGT) acts as a ROS sensor in hepatocellular carcinoma (HCC) [4][10]. - ROS-induced oxidation activates OGT, which then modifies the transcription factor FOXK2, promoting its nuclear translocation and upregulating the expression of the key gene SLC7A11, thereby inhibiting ferroptosis and enhancing chemotherapy resistance in liver cancer cells [4][8]. Group 2: Implications for Cancer Treatment - The research elucidates a ROS-mediated oxidation-O-GlcNAcylation cascade that integrates ROS signaling, O-GlcNAc modification, and FOXK2-mediated transcriptional regulation of SLC7A11, contributing to resistance against ferroptosis and chemotherapy [10]. - Targeting this mechanism may provide a novel approach to reactivate ferroptosis, offering new strategies to overcome cancer resistance [10].