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Related Experiment Video

Updated: Jan 12, 2026

Vasodilation of Isolated Vessels and the Isolation of the Extracellular Matrix of Tight-skin Mice
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ZNF334 truncation mutation drives cold-induced autoinflammation.

Joung-Liang Lan1,2,3, Shih-Hsin Chang3,4, Yi-Hua Lai1,2,3

  • 1College of Medicine, China Medical University, Taichung, Taiwan.

EMBO Molecular Medicine
|October 31, 2025
PubMed
Summary

Zinc finger protein 334 (ZNF334) regulates cold-induced inflammation. A ZNF334 mutation impairs heat shock protein 90 (Hsp90) interaction, causing autoinflammatory disease. Hsp90 inhibitors may treat cold-induced inflammatory conditions.

Keywords:
AutoinflammationColdMutationSensorineural Hearing LossZNF334

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Area of Science:

  • Immunology
  • Genetics
  • Molecular Biology

Background:

  • The function of zinc finger protein 334 (ZNF334) in immunity is unclear.
  • Autoinflammatory diseases can be triggered by environmental factors like cold exposure.

Purpose of the Study:

  • To investigate the role of ZNF334 in cold-induced inflammation and autoinflammatory disease.
  • To elucidate the molecular mechanisms underlying ZNF334 deficiency-related pathology.

Main Methods:

  • Identified a ZNF334 truncation mutation in a patient with cold-induced autoinflammatory disease.
  • Utilized patient-derived monocytes and CRISPR/Cas9-edited THP-1 cells.
  • Analyzed protein interactions, cellular stress responses, and inflammatory signaling pathways.

Main Results:

  • The ZNF334 mutation disrupted ZNF334-Hsp90 interaction, reducing cold stress regulators (Hsp90, TRPM8).
  • Mutation led to ER stress, impaired redox homeostasis, and increased cold-induced NF-κB activation.
  • Monocytes from the patient exhibited enhanced secretion of pro-inflammatory extracellular vesicles containing mitochondria.
  • Cold avoidance improved patient symptoms; Hsp90 inhibition in cells reduced cold-induced inflammation.

Conclusions:

  • ZNF334 is crucial for regulating cold-induced inflammation and oxidative stress.
  • Hsp90 ATPase inhibitors show potential for treating autoinflammatory diseases triggered by cold exposure.