Inhibition of CD82 improves colitis by increasing NLRP3 deubiquitination by BRCC3.

Abstract

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.

• Authors: Jae-Sung Kim, Hyo Keun Kim, Joongho Lee, Sein Jang, Euni Cho, Seok-Jun Mun, Seokhyun Yoon, Chul-Su Yang
• Journal: Cellular & molecular immunology (Cell Mol Immunol) Vol. 20 Issue 2 Pg. 189-200 (02 2023) ISSN: 2042-0226 [Electronic] China
• PMID: 36600050 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023. The Author(s), under exclusive licence to CSI and USTC.

Chemical References

• Dextran Sulfate
• Inflammasomes
• NLR Family, Pyrin Domain-Containing 3 Protein
• Nlrp3 protein, mouse
• Cd82 antigen, mouse
• BRCC3 protein, mouse

Topics

• Animals
• Mice
• Colitis (metabolism)
• Dextran Sulfate
• Inflammasomes (metabolism)
• Mice, Inbred C57BL
• NLR Family, Pyrin Domain-Containing 3 Protein (metabolism)