Highlights

• The p53^R211* mutation demonstrated a remarkable ability to improve inflammatory arthritis in AIA rats.
• This mutation exerts its beneficial effects by suppressing the TBK1-IRF3-STING innate immune pathway, indicating that this mutation is a specific target for modulating the immune response in patients with arthritis.
• This study provides a new perspective on the role of p53 mutations in autoimmune diseases such as rheumatoid arthritis.

Summary

This research investigated the role of a specific mutant of the p53 gene, p53^R211*, in the context of rheumatoid arthritis (RA). Usually, p53 mutations are associated with cancer progression, where they facilitate drug resistance and immune evasion.

This research utilized a rat model of adjuvant-induced arthritis (AIA) to examine how p53^R211* overexpression influences this disease. These findings revealed that this particular mutation improved inflammatory arthritis in rats. This effect includes the suppression of T-cell activation, a reduction in T helper 17 cell infiltration, and a decrease in the production of proinflammatory cytokines.

Mechanistically, p53^R211* interacts with TANK-binding kinase 1 (TBK1) and interferes with the TBK1–interferon regulatory factor 3 (IRF3)–stimulator of interferon genes (STING) immune pathway. These results suggest a novel function of the p53^R211* mutation in modulating immune responses in RA, offering potential insights into new anti-inflammatory targets for treatment.

Y. Zeng et al., “Mutant p53^R211* ameliorates inflammatory arthritis in AIA rats via inhibition of TBK1-IRF3 innate immune response,” Inflamm. Res., vol. 72, no. 12, pp. 2199–2219, Dec. 2023, doi: