How interactions between oxidized DNA and the NLRP3 inflammasome fuel inflammatory disease

Trends Biochem Sci. 2025 Oct;50(10):931-944. doi: 10.1016/j.tibs.2025.07.007. Epub 2025 Aug 28.

Abstract

Recent discoveries have emphasized the critical role of oxidized DNA (ox-DNA) in inflammation and immune regulation. Produced during oxidative stress from infection or tissue damage, ox-DNA activates signaling pathways that drive the release of proinflammatory cytokines, specifically engaging the NLRP3 inflammasome, a key player in cytokine maturation and host defense. NLRP3 is increasingly implicated in inflammatory and autoimmune diseases, with ox-DNA recognized as a central activator of this inflammasome. This review examines the role of ox-DNA in inflammasome activation, its broader impact on inflammatory processes, and promising therapeutic approaches targeting ox-DNA through both immunological and structural lenses. These insights highlight ox-DNA's relevance in inflammation and offer potential avenues for the treatment of a range of immune-related disorders.

Keywords: DNA damage; inflammasome; inflammation; innate immunity; mitochondrial dysregulation.

Publication types

  • Review

MeSH terms

  • Animals
  • DNA* / immunology
  • DNA* / metabolism
  • Humans
  • Inflammasomes* / immunology
  • Inflammasomes* / metabolism
  • Inflammation* / immunology
  • Inflammation* / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein* / immunology
  • NLR Family, Pyrin Domain-Containing 3 Protein* / metabolism
  • Oxidation-Reduction
  • Oxidative Stress
  • Signal Transduction

Substances

  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Inflammasomes
  • DNA
  • NLRP3 protein, human