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Attenuation of rheumatoid arthritis through the inhibition of caspase3/GSDME-mediated pyroptosis induced by TNF-α

Attenuation of rheumatoid arthritis through the inhibition o...

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第十四届全国免疫学学术大会

作者： Zeqing Zhai Fangyuan Yang Wenchao Xu jiaochan han Guihu Luo Yehao Li Jian Zhuang Hongyu Jie Xing Li Xingliang Shi han Xinai Xiaoqing Luo Rui Song Yonghong Chen Jianheng Liang Shufan Wu Yi He Erwei Sun 南方医科大学第三附属医院(广东省骨科研究院)风湿免疫科

To determine the role of gasdermin E(GSDME)-mediated pyroptosis in the pathogenesis and progression of rheumatoid arthritis(RA), and explore the potential therapeutic targets for ***: The expression and activation of caspase3 and GSDME in the synovium, macrophages, and monocytes of RA patients was detected by immunohistochemistry, immunofluorescence, and western blot analysis. The correlation of activated GSDME with RA disease activity was evaluated. The pyroptotic ability of monocytes from RA patients was also tested. In addition, the effect of TNF-α on caspase3/GSDME-mediated pyroptosis of monocytes and macrophages was investigated. Furthermore, mice lacking Gsdme were subjected to collagen-induced arthritis, and the incidence and severity of arthritis was ***: Monocytes and synovial macrophages from RA patients showed increased expression of activated caspase3,GSDME, and GSDME-N. The expression of GSDME-N in monocytes from RA patients correlated positively with the disease activity. Monocytes from RA patients with higher GSDME levels were more susceptible to pyroptosis. Furthermore, TNF-α induced pyroptosis in monocytes and macrophages by activating the caspase3/GSDME pathway. The use of a caspase3 inhibitor and silencing of GSDME significantly blocked TNF-α–induced pyroptosis. Gsdme deficiency effectively alleviated arthritis in a collagen-induced arthritis mice ***: These Results support a pathogenic role of GSDME in RA and provide an alternative mechanism for RA pathogenesis involving TNF-α, which activates GSDME-mediated pyroptosis of monocytes and macrophages in RA. In addition, targeting GSDME might be a potential therapeutic approach for RA.

关键词： Rheumatoid Arthritis(RA) Pyroptosis Gasdermin E(GSDME) Tumor necrosis factor α(TNF-α) Collagen-Induced Arthritis(CIA)

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