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Updated: Apr 11, 2026
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Detection of Inflammasome Activation and Pyroptotic Cell Death in Murine Bone Marrow-derived Macrophages
Published on: May 21, 2018
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MEX3B is a positive pan-inflammasome regulator
Biorxiv : the Preprint Server for Biology
|April 10, 2026
Summary
Muscle Excess 3B (MEX3B), an RNA-binding protein, regulates inflammasomes controlling immune responses. Depleting MEX3B inhibits inflammasome activation, pyroptosis, and cytokine release, suggesting it as a therapeutic target for inflammation.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- Inflammasomes activate inflammatory caspases, driving pyroptosis and immune responses against microbes.
- Tight regulation of inflammasomes is crucial to prevent sepsis and autoimmune diseases.
- Posttranslational regulation of inflammatory caspases is not well understood.
Purpose of the Study:
- To identify novel regulators of inflammatory caspases and inflammasome activation.
- To investigate the role of ubiquitin ligases in inflammasome posttranslational regulation.
Main Methods:
- Generated 375 CRISPR-Cas9 ubiquitin ligase knockout lines for unbiased screening.
- Assessed inflammasome activation, pyroptosis, and cytokine secretion in human cells and murine macrophages.
- Investigated the functional requirement of MEX3B's RNA-binding and ubiquitin ligase activities.
Main Results:
- Identified Muscle Excess 3B (MEX3B), an RNA-binding protein and ubiquitin ligase, as a positive regulator of the caspase-4 inflammasome.
- Genetic depletion of MEX3B inhibited caspase-4, NLRP3, and NLRC4 inflammasomes.
- MEX3B's role in regulating inflammasomes required its RNA-binding activity, not its ubiquitin ligase activity.
Conclusions:
- MEX3B acts as a pan-inflammasome regulator, impacting caspase activation, pyroptosis, and cytokine secretion.
- MEX3B is a potential therapeutic target for treating inflammatory conditions.
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