波恩大学Christoph Wilhelm小组在研究中取得进展。他们探明了对铁死亡的耐受促进了过敏性气道炎症中的脂质代谢和致病性2型免疫。2025年12月10日出版的《免疫学》发表了这项成果。

该课题组发现在变应性气道炎症中，致病性ILC2s依赖胱氨酸增强代谢灵活性和生存。胱氨酸获取促进谷胱甘肽（GSH）的合成，与谷胱甘肽过氧化物酶4 （GPX4）和硫氧还蛋白还原酶1 （TXNRD1）的表达增加一起，通过对抗脂质过氧化和活性氧（ROS），赋予铁死亡抗性。这种适应能够加速脂质获取和代谢，促进ILC2和T辅助型2 （Th2）细胞的扩增。相反，消融ILC2s中的GPX4和TXNRD1或药理抑制TXNRD1可抑制脂质代谢并阻止ILC2在过敏原诱导的气道炎症中的积累。这表明，对抗氧化系统的依赖增加代表了一种代谢脆弱性，可以用于治疗哮喘。

据介绍，2型先天淋巴样细胞（ILC2s）对于维持和保护屏障组织至关重要，但它们也会引发慢性炎症，这一过程与代谢活动的改变有关。识别和靶向驱动ILC2介导的炎症的代谢途径可以恢复组织稳态。

附：英文原文

Title: Tolerance to ferroptosis facilitates lipid metabolism and pathogenic type 2 immunity in allergic airway inflammation

Author: Chantal Wientjens, Maria Doverman, Jelena Zurkovic, Tushar More, Jayagopi Surendar, Svetozar Nesic, Carola Sarici, Timon D. Utecht, Johanna Pohl, Jonathan Pollock, David Voehringer, Karsten Hiller, Christoph Thiele, Christoph Wilhelm

Issue&Volume: 2025-12-10

Abstract: Type 2 innate lymphoid cells (ILC2s) are essential for maintaining and protecting barrier tissues, but they also drive chronic inflammation, a process associated with altered metabolic activity. Identifying and targeting the metabolic pathways driving ILC2-mediated inflammation could restore tissue homeostasis. Here, we find that in allergic airway inflammation, pathogenic ILC2s rely on cystine for enhanced metabolic flexibility and survival. Cystine acquisition fuels glutathione (GSH) synthesis, which, together with increased expression of glutathione peroxidase 4 (GPX4) and thioredoxin reductase 1 (TXNRD1), confers resistance to ferroptosis by counteracting lipid peroxidation and reactive oxygen species (ROS). This adaptation enables accelerated lipid acquisition and metabolism, fostering ILC2 and T helper type 2 (Th2) cell expansion. Conversely, ablation of GPX4 and TXNRD1 in ILC2s or pharmacological inhibition of TXNRD1 constrains lipid metabolism and prevents ILC2 accumulation in allergen-induced airway inflammation. This demonstrates that increased reliance on antioxidant systems represents a metabolic vulnerability that can be exploited therapeutically to treat asthma.

DOI: 10.1016/j.immuni.2025.11.018

Source: https://www.cell.com/immunity/abstract/S1074-7613(25)00520-5