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Updated: Sep 15, 2025
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Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
Published on: March 15, 2024
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The NF-κB-SLC7A11 axis regulates ferroptosis sensitivity in inflammatory macrophages
Mengjie Yang1,2, Xiaowei Chen2, Xiran Hu2
1Department of Urology, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, Hubei, China.
Cell Insight
|July 18, 2025
Summary
M1 macrophages resist ferroptosis via the cystine/glutamate antiporter SLC7A11. This mechanism, regulated by Toll-like receptor 4 (TLR4) and NF-κB, controls glutathione production and macrophage death.
Area of Science:
- Immunology
- Cell Biology
- Metabolism
Background:
- M1-polarized macrophages are resistant to ferroptosis, a cell death pathway.
- The molecular mechanisms underlying this resistance are not fully understood.
Purpose of the Study:
- To identify key metabolic genes mediating ferroptosis resistance in M1 macrophages.
- To elucidate the signaling pathway regulating ferroptosis sensitivity in M1 macrophages.
Main Methods:
- CRISPR-based functional screening of metabolic genes.
- Transcriptomics analysis.
- Investigated the role of SLC7A11 in ferroptosis using genetic ablation.
Main Results:
- Identified SLC7A11 as a critical mediator of ferroptosis resistance in M1 macrophages.
- LPS-TLR4 signaling activates NF-κB, upregulating SLC7A11 expression.
- SLC7A11 enhances glutathione synthesis, conferring ferroptosis resistance.
- Genetic deletion of SLC7A11 sensitizes M1 macrophages to ferroptosis.
Conclusions:
- The RELA-SLC7A11 axis is a key metabolic regulator of macrophage ferroptosis.
- Targeting this pathway could modulate macrophage function in inflammatory diseases.
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