Department of Pediatrics, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, 510655, China.
Department of Laboratory Medicine, Nanfang Hospital Baiyun Branch, Southern Medical University, Guangzhou, 510420, China; State Key Laboratory of Bioactive Molecules and Druggability Assessment, The Biomedical Translational Research Institute, Health Science Center (School of Medicine), Jinan University, Guangzhou, 510632, China; Key Laboratory of Viral Pathogenesis & Infection Prevention and Control (Jinan University), Ministry of Education, Guangzhou, 510632, China.
Redox Biol. 2024 Sep;75:103303. doi: 10.1016/j.redox.2024.103303. Epub 2024 Aug 8.
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.
坏死性小肠结肠炎（NEC）肠组织中 Treg 数量的显著下降，导致过度炎症和坏死，但确切的潜在因素仍不清楚。铁死亡，一种源于脂质氧化还原代谢紊乱的新型细胞死亡，是本研究的重点。具体来说，本研究深入研究了 NEC 中 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 细胞减少与铁死亡的关系，我们从多个角度分析了它们之间的关系。我们构建了一种 Treg 细胞特异性 Gpx4 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，监测肠道炎症损伤的后续改善。
NEC 中 Treg 细胞的减少归因于 GPX4 表达减少引起的铁死亡。Gpx4 缺陷型 Treg 细胞表现出受损的免疫抑制功能，易发生铁死亡。这种 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，从而缓解 NEC 中的肠道损伤和炎症。此外，维生素 E 通过上调 GPX4 的表达增强了 Treg 细胞的抗脂质过氧化能力。
在 NEC 中，Treg 细胞的铁死亡是导致肠道组织损伤和炎症反应加剧的重要因素。GPX4 是 Treg 细胞存活和功能的关键。维生素 E 具有减轻 Treg 细胞铁死亡的能力，从而增加其数量和功能，在减轻 NEC 中肠道组织损伤和炎症反应方面发挥着重要作用。
