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Related Experiment Video

Updated: Apr 11, 2026

Detection of Inflammasome Activation and Pyroptotic Cell Death in Murine Bone Marrow-derived Macrophages
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MEX3B is a positive pan-inflammasome regulator.

Jason G Cahoon, Tingting Geng, Duomeng Yang

    Biorxiv : the Preprint Server for Biology
    |April 10, 2026
    PubMed
    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.

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    Visualization of Inflammatory Caspases Induced Proximity in Human Monocyte-Derived Macrophages
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    Visualization of Inflammatory Caspases Induced Proximity in Human Monocyte-Derived Macrophages

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    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.