The notable decline in the number of Tregs within Necrotizing enterocolitis (NEC) intestinal tissues，contribute to excessive inflammation and necrosis, yet the precise underlying factors remain enigmatic. Ferroptosis, a novel cell death stemming from a disrupted lipid redox metabolism, is the focus of this investigation. Specifically, this study delves into the ferroptosis of Treg cells in the context of NEC and observes the protective effects exerted by vitamin E intervention, which aims to mitigate ferroptosis of Treg cells. To investigate the reduction of Treg cells in NEC intestine, we analyzed its association with ferroptosis from multiple angles. We constructed a mouse with a specific knockout of Gpx4 in Treg cells, aiming to examine the impact of Treg cell ferroptosis on NEC intestinal injury and localized inflammation. Ultimately, we employed vitamin E treatment to mitigate ferroptosis in NEC intestine's Treg cells, monitoring the subsequent amelioration in intestinal inflammatory damage. The diminution of Treg cells in NEC is attributed to ferroptosis stemming from diminished GPX4 expression. Gpx4-deficient Treg cells exhibit impaired immunosuppressive function and are susceptible to ferroptosis. This ferroptosis of Treg cells exacerbates intestinal damage and inflammatory response in NEC. Notably, Vitamin E can inhibit the ferroptosis of Treg cells, subsequently alleviating intestinal damage and inflammation in NEC. Additionally, Vitamin E bolsters the anti-lipid peroxidation capability of Treg cells by upregulating the expression of GPX4. In the context of NEC, the ferroptosis of Treg cells represents a significant factor contributing to intestinal tissue damage and an exaggerated inflammatory response. GPX4 is pivotal for the viability and functionality of Treg cells. Vitamin E exhibits the capability to mitigate the ferroptosis of Treg cells, thereby enhancing their number and function, which plays a crucial role in mitigating intestinal tissue damage and inflammatory response in NEC.

中文翻译：

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维生素E和GPX4协同保护Treg细胞免于铁死亡并减轻坏死性小肠结肠炎中的肠道炎症损伤


坏死性小肠结肠炎 (NEC) 肠道组织中 Treg 数量显着下降，导致过度炎症和坏死，但确切的潜在因素仍然是个谜。铁死亡是一种由脂质氧化还原代谢紊乱引起的新型细胞死亡，是本次研究的重点。具体来说，本研究深入研究了 NEC 背景下 Treg 细胞的铁死亡，并观察了维生素 E 干预所产生的保护作用，旨在减轻 Treg 细胞的铁死亡。为了研究NEC肠道中Treg细胞的减少，我们从多个角度分析了其与铁死亡的关系。我们构建了Treg细胞中Gpx4特异性敲除的小鼠，旨在研究Treg细胞铁死亡对NEC肠道损伤和局部炎症的影响。最终，我们采用维生素 E 治疗来减轻 NEC 肠道 Treg 细胞的铁死亡，监测随后肠道炎症损伤的改善情况。 NEC 中 Treg 细胞的减少归因于 GPX4 表达减少引起的铁死亡。 Gpx4 缺陷的 Treg 细胞表现出免疫抑制功能受损，并且容易发生铁死亡。 Treg 细胞的铁死亡加剧了 NEC 中的肠道损伤和炎症反应。值得注意的是，维生素 E 可以抑制 Treg 细胞的铁死亡，从而减轻 NEC 中的肠道损伤和炎症。此外，维生素 E 通过上调 GPX4 的表达来增强 Treg 细胞的抗脂质过氧化能力。在 NEC 的背景下，Treg 细胞的铁死亡是导致肠道组织损伤和过度炎症反应的一个重要因素。 GPX4 对于 Treg 细胞的活力和功能至关重要。维生素E具有减轻Treg细胞铁死亡的能力，从而增强其数量和功能，这在减轻NEC肠道组织损伤和炎症反应中发挥着至关重要的作用。