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Updated: Jun 22, 2026
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Depletion and Reconstitution of Macrophages in Mice
Published on: August 1, 2012
39.7K
Inflammatory macrophages reprogram to immunosuppression by reducing mitochondrial translation.
Marlies Cortés1, Agnese Brischetto2, M C Martinez-Campanario2
1Group of Gene Regulation in Stem Cells, Cell Plasticity, Differentiation, and Cancer, IDIBAPS, 08036, Barcelona, Spain. mcortesh@recerca.clinic.cat.
Nature Communications
|November 18, 2023
Summary
The plasticity factor ZEB1 is crucial for both initiating and resolving inflammation by reprogramming macrophages. Metformin mimics ZEB1
Area of Science:
- Immunology
- Cell Biology
- Metabolism
Background:
- Inflammation can resolve or become chronic, driven by immune cell reprogramming.
- The anti-diabetic drug Metformin impacts inflammation via poorly understood mechanisms.
Purpose of the Study:
- To investigate the role of ZEB1 in Metformin's anti-inflammatory effects.
- To elucidate ZEB1's function in macrophage metabolic reprogramming during inflammation resolution.
Main Methods:
- Utilized ZEB1-deficient mice (myeloid-specific knockout).
- Analyzed human patient samples.
- Investigated macrophage metabolic and mitochondrial changes.
- Assessed mTORC1 signaling and protein translation.
Main Results:
- Metformin's anti-inflammatory effects are dependent on ZEB1 expression in macrophages.
- ZEB1 is essential for both initiating and resolving inflammation by promoting immunosuppression.
- ZEB1 modulates mitochondrial content via autophagy and inhibits mitochondrial translation.
- Metformin mimics ZEB1-induced metabolic reprogramming, inhibiting mTORC1 signaling and mitochondrial translation.
Conclusions:
- ZEB1 drives myeloid cell metabolic plasticity, influencing inflammation and immunosuppression.
- Targeting ZEB1 offers a potential strategy for modulating inflammatory and immunosuppressive conditions.
