PDF(Pubmed)
Abstract：
BACKGROUND: 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.
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.
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.
摘要：
背景：坏死性小肠结肠炎（NEC）肠组织中Treg的数量显著下降，导致过度的炎症和坏死，然而，确切的潜在因素仍然是神秘的。Ferroptosis,一种由脂质氧化还原代谢中断引起的新型细胞死亡，是这次调查的重点.具体来说,这项研究探讨了NEC背景下Treg细胞的铁凋亡，并观察了维生素E干预的保护作用，旨在减轻Treg细胞的铁凋亡。
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。
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。
