NOTE, original article title: Attenuation of rheumatoid arthritis through the inhibition of tumor necrosis factor–induced caspase 3/gasdermin E–mediated pyroptosis

Findings lend support to the idea that gasdermin E (GSDME) has a pathogenic role in rheumatoid arthritis (RA), and an alternative mechanism is suggested for RA pathogenesis implicating tumor necrosis factor (TNF), which activates GSDME-mediated pyroptosis of monocytes and macrophages in RA. Additionally, targeting GSDME might represent a potential therapeutic approach for RA.

• Increased expression of activated caspase 3, GSDME, and the N-terminal fragment of GSDME (GSDME-N) was demonstrated by monocytes and synovial macrophages from RA patients, vs cells from healthy controls.

• A positive correlation was found between expression of GSDME-N in monocytes from RA patients and disease activity.

• Greater susceptibility to pyroptosis was exhibited by monocytes from RA patients with higher GSDME levels.

• In monocytes and macrophages, pyroptosis was caused by TNF by activating the caspase 3/GSDME pathway.

• TNF-induced pyroptosis was shown to be significantly blocked by a caspase 3 inhibitor and silencing of GSDME.

• A mouse model of collagen-induced arthritis showed that effective alleviation of arthritis was brought about by GSDME deficiency.