Related Experiment Video

Updated: Mar 20, 2026

Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells
09:04

Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells

Published on: May 22, 2014

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Cofilin-1 is a redox-sensitive guard of the NLRP3 inflammasome

Yong Hwan Park1,2,3,4, Ezgi D Batu1, Brynja Matthiasardottir1,5

  • 1Inflammatory Disease Section, Medical Genetics Branch, National Human Genome Research Institute, Bethesda, MD, USA.

Nature Immunology
|March 19, 2026
PubMed

Insights

Cofilin-1 negatively regulates the NLRP3 inflammasome, a key player in autoinflammatory diseases. Peptides derived from cofilin-1 show potential for treating cryopyrin-associated periodic syndromes (CAPS).

Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • Cryopyrin-associated periodic syndromes (CAPS) are autoinflammatory diseases caused by NLRP3 mutations.
  • Reactive oxygen species (ROS) are crucial for NLRP3 inflammasome activation.

Purpose of the Study:

  • To investigate the role of cofilin-1 as a regulator of the NLRP3 inflammasome.
  • To explore the therapeutic potential of cofilin-1-derived peptides for CAPS.

Main Methods:

  • Protein binding assays to assess cofilin-1 and NLRP3 interaction.
  • ROS-mediated oxidation studies of cofilin-1.
  • Peptide-based inhibition assays using NLRP3 activators and CAPS models.
  • Bioinformatic structural analyses.

Main Results:

  • Cofilin-1 directly binds NLRP3 in resting cells and dissociates upon ROS-induced oxidation.
  • CAPS-associated NLRP3 mutants show decreased binding to cofilin-1.
  • Specific cofilin-1 residues (101-104) are critical for NLRP3 interaction.
  • Oxidation-independent cofilin-1 peptides suppressed inflammasome activation in vitro and in CAPS models.

Conclusions:

  • Cofilin-1 acts as a negative regulator of NLRP3 inflammasome activation, modulated by ROS.
  • Cofilin-1-derived peptides represent a promising therapeutic strategy for patients with CAPS, particularly those unresponsive to existing treatments.

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