Highlights

• This study demonstrated that the accumulation of DNA fragments, which increases with age, promotes abnormal immune system activation in individuals with RA.
• Overexpression of TREX1, which is downregulated in the context of RA, can mitigate synovial inflammation, suggesting that TREX1 is a potential therapeutic target.
• This research revealed a novel connection between DNA fragment accumulation due to TREX1 downregulation and the improvement of RA symptoms.

Summary

This research investigated the role of self-DNA accumulation in the progression of rheumatoid arthritis (RA). This study revealed that DNA fragments accumulate as individuals age and can promote abnormal immune system activation.

The activity of the enzyme TREX1 influences this process. When TREX1 is downregulated, the level of circulating free DNA increases, leading to improved RA symptoms. In a rat model, overexpression of TREX1 reduced inflammation, while TREX1 deletion worsened inflammation. This connection is partly regulated by the transcription factor AP-1, which impacts TREX1 expression and inflammatory responses.

This research underscores the significance of DNA fragments as inflammatory mediators in RA. Moreover, managing these fragments through TREX1 could be a novel strategy for preventing or treating RA. This approach could alleviate the burden of RA, offering insights into its pathogenesis linked with aging.

W.-D. Luo et al., “Age-related self-DNA accumulation may accelerate arthritis in rats and in human rheumatoid arthritis,” Nat Commun, vol. 14, no. 1, p. 4394, Jul. 2023, doi: 10.1038/s41467-023-40113-3