首页|Inhibition of CD82 improves colitis by increasing NLRP3 deubiquitination by BRCC3

Inhibition of CD82 improves colitis by increasing NLRP3 deubiquitination by BRCC3

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CD82 is a transmembrane protein that is involved in cancer suppression and activates immune cells;however,information on the NLRP3 inflammasome is limited.Herein,we show that although CD82 suppressed the activation of the NLRP3 inflammasome in vivo and in vitro,CD82 deficiency decreased the severity of colitis in mice.Furthermore,two binding partners of CD82,NLRP3 and BRCC3,were identified.CD82 binding to these partners increased the degradation of NLRP3 by blocking BRCC3-dependent K63-specific deubiquitination.Previous studies have shown that CD82-specific bacteria in the colon microbiota called Bacteroides vulgatus(B.vulgatus)regulated the expression of CD82 and promoted the activation of the NLRP3 inflammasome.Accordingly,we observed that B.vulgatus administration increased mouse survival by mediating CD82 expression and activating NLRP3 in mice with colitis.Overall,this study showed that CD82 suppression reduced the pathogenesis of colitis by elevating the activation of the NLRP3 inflammasome through BRCC3-dependent K63 deubiquitination.Based on our findings,we propose that B.vulgatus is a novel therapeutic candidate for colitis.

CD82NLRP3BRCC3ColitisInflammation

Jae-Sung Kim、Hyo Keun Kim、Joongho Lee、Sein Jang、Euni Cho、Seok-Jun Mun、Seokhyun Yoon、Chul-Su Yang

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Department of Bionano Technology,Hanyang University,Seoul 04673,Korea

Institute of Natural Science&Technology,Hanyang University,Ansan 15588,Korea

Department of Molecular and Life Science,Hanyang University,Ansan 15588,Korea

Center for Bionano Intelligence Education and Research,Ansan 15588,Korea

Department of Computer Science,College of SW Convergence,Dankook University,Yongin 16890,Korea

Department of Electronics&Electrical Engineering,College of Engineering,Dankook University,Yongin 16890,Korea

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NRF grant funded by the Korean government(MSIP)research fund of Hanyang University

2021R1A4A5032463HY-2021

2023

10.1038/s41423-022-00971-1

中国免疫学杂志(英文版)
中国免疫学会

中国免疫学杂志(英文版)

CSTPCDCSCDSCI
影响因子：0.731
ISSN：1672-7681
年,卷(期)：2023.20(2)
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