Cytoplasmic DNA and AIM2 inflammasome in RA: where they come from and where they go?

Front Immunol. 2024 Oct 10:15:1343325. doi: 10.3389/fimmu.2024.1343325. eCollection 2024.

Abstract

Rheumatoid arthritis is a chronic autoimmune disease of undetermined etiology characterized by symmetric synovitis with predominantly destructive and multiple joint inflammation. Cytoplasmic DNA sensors that recognize protein molecules that are not themselves or abnormal dsDNA fragments play an integral role in the generation and perpetuation of autoimmune diseases by activating different signaling pathways and triggering innate immune signaling pathways and host defenses. Among them, melanoma deficiency factor 2 (AIM2) recognizes damaged DNA and double-stranded DNA and binds to them to further assemble inflammasome, initiating the innate immune response and participating in the pathophysiological process of rheumatoid arthritis. In this article, we review the research progress on the source of cytoplasmic DNA, the mechanism of assembly and activation of AIM2 inflammasome, and the related roles of other cytoplasmic DNA sensors in rheumatoid arthritis.

Keywords: AIM2; cytosolic DNA; inflammasome; pyroptosis; rheumatoid arthritis.

Publication types

  • Review

MeSH terms

  • Animals
  • Arthritis, Rheumatoid* / immunology
  • Arthritis, Rheumatoid* / metabolism
  • Cytoplasm* / immunology
  • Cytoplasm* / metabolism
  • DNA* / immunology
  • DNA* / metabolism
  • DNA-Binding Proteins* / genetics
  • DNA-Binding Proteins* / metabolism
  • Humans
  • Immunity, Innate
  • Inflammasomes* / immunology
  • Inflammasomes* / metabolism
  • Signal Transduction

Substances

  • Inflammasomes
  • AIM2 protein, human
  • DNA-Binding Proteins
  • DNA

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China (No. 82060891), Youth Science and Technology Fund (No.23JRRA1686), Project of Zheng’s Acupuncture Academic Schools of Heritage Studio, Gansu Province, State Administration of TCM (No. 2305135901).