METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
方法: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中毒的关系。我们构建了在Treg细胞中具有Gpx4特异性敲除的小鼠,目的研究Treg细胞凋亡对NEC肠损伤和局部炎症的影响。最终,我们采用维生素E治疗减轻NEC肠Treg细胞的铁凋亡,监测肠道炎症损伤的后续改善。
结果:NEC中Treg细胞的减少归因于源于GPX4表达减少的铁死亡。Gpx4缺陷型Treg细胞表现出受损的免疫抑制功能并且易受铁凋亡的影响。Treg细胞的这种铁凋亡加剧了NEC中的肠损伤和炎症反应。值得注意的是,维生素E可以抑制Treg细胞的铁凋亡,随后缓解NEC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。
结论:在NEC的背景下,Treg细胞的铁凋亡是导致肠组织损伤和过度炎症反应的重要因素。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细胞铁凋亡的能力,从而提高它们的数量和功能,在减轻NEC的肠组织损伤和炎症反应中起着至关重要的作用。