TNF antagonist sensitizes synovial fibroblasts to ferroptotic cell death in collagen-induced arthritis mouse models

Ferroptosis is a nonapoptotic cell death process that requires cellular iron and the accumulation of lipid peroxides. In progressive rheumatoid arthritis (RA), synovial fibroblasts proliferate abnormally in the presence of reactive oxygen species (ROS) and elevated lipid oxidation. Here we show, using a collagen-induced arthritis (CIA) mouse model, that imidazole ketone erastin (IKE), a ferroptosis inducer, decreases fibroblast numbers in the synovium. Data from single-cell RNA sequencing further identify two groups of fibroblasts that have distinct susceptibility to IKE-induced ferroptosis, with the ferroptosis-resistant fibroblasts associated with an increased TNF-related transcriptome. Mechanistically, TNF…

• NN
  National Natural Science Foundation of China

  Awards: P30 CA008748, 82022059
• NC
  National Cancer Institute

  Awards: Core Grant P30 CA008748, CA008748, P30 CA008748, Grant P30 CA008748