ArticleJournal of immunology (Baltimore, Md. : 1950)2024
Gpx4 Regulates Invariant NKT Cell Homeostasis and Function by Preventing Lipid Peroxidation and Ferroptosis.
Article in Journal of immunology (Baltimore, Md. : 1950), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Exploring Ferroptosis: A Key Mechanism in Respiratory System Diseases and its Therapeutic Potential.Applied biochemistry and biotechnology · 2026Review
- Mechanisms driving resistance to oxidative stress during endometrial stromal cell decidualization†.Biology of reproduction · 2026Review
- Ferroptosis and immunity: rewiring the tumor microenvironment for therapy.RSC advances · 2026Review
- Interplay between natural killer cells and ferroptosis: novel insights in tumor immunity and therapeutic potential.Cell communication and signaling : CCS · 2026Review
- Targeting glutathione peroxidase 4 in ferroptosis: from immune regulation to pharmacological development and translational applications.Frontiers in pharmacology · 2026Review
- Potential crosstalk between ferroptosis and immunosenescence in osteoarthritis: evidence integration and translational insights from the osteoimmune microenvironment.Frontiers in immunology · 2026Review
- Metabolic control of innate-like T cells.Nature reviews. Immunology · 2026Review
- The emerging role of ferroptosis in the pathological development and progression of sepsis.Military Medical Research · 2025Review
- [Research progress on the role of invariant natural killer T cells in immune-mediated liver injury].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2025Review
- P-glycoprotein expression skews mitochondrial dye measurements in T cells.Frontiers in immunology · 2025Article
- Elevated Type 2 Inflammatory Factors, Th2/Th1 Balanced Status, and Exosomes as a Marker of Severity in Chronic Actinic Dermatitis.Mediators of inflammation · 2025Article
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Authors and funding
10 authors.
Funding
Abstract
Invariant NKT (iNKT) cells are a group of innate-like T cells that plays important roles in immune homeostasis and activation. We found that iNKT cells, compared with CD4+ T cells, have significantly higher levels of lipid peroxidation in both mice and humans. Proteomic analysis also demonstrated that iNKT cells express higher levels of phospholipid hydroperoxidase glutathione peroxidase 4 (Gpx4), a major antioxidant enzyme that reduces lipid peroxidation and prevents ferroptosis. T cell-specific deletion of Gpx4 reduces iNKT cell population, most prominently the IFN-γ-producing NKT1 subset. RNA-sequencing analysis revealed that IFN-γ signaling, cell cycle regulation, and mitochondrial function are perturbed by Gpx4 deletion in iNKT cells. Consistently, we detected impaired cytokine production, elevated cell proliferation and cell death, and accumulation of lipid peroxides and mitochondrial reactive oxygen species in Gpx4 knockout iNKT cells. Ferroptosis inhibitors, iron chelators, vitamin E, and vitamin K2 can prevent ferroptosis induced by Gpx4 deficiency in iNKT cells and ameliorate the impaired function of iNKT cells due to Gpx4 inhibition. Last, vitamin E rescues iNKT cell population in Gpx4 knockout mice. Altogether, our findings reveal the critical role of Gpx4 in regulating iNKT cell homeostasis and function, through controlling lipid peroxidation and ferroptosis.
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