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Updated: Sep 21, 2025

Detection of Inflammasome Activation and Pyroptotic Cell Death in Murine Bone Marrow-derived Macrophages
Published on: May 21, 2018
The regulation of NLRP3 inflammasome activation by CCDC50-mediated autophagy
Panpan Hou1, Tian Tian2, Penghui Jia1
1MOE Key Laboratory of Tropical Disease Control, Centre for Infection and Immunity Study (CIIS), School of Medicine, Sun Yat-sen University, Shenzhen, China.
Abstract:
The assembly of the NLRP3 inflammasome can be initiated by a wide range of stimuli including exogenous infection as well as endogenous damage. Therefore, the tight regulation of the NLRP3 inflammasome is crucial for the host to resist microbial invasion and maintain homeostasis. Our recent work has identified a negative regulator of NLRP3-mediated inflammation, namely CCDC50 (coiled-coil domain containing protein 50). CCDC50 can be induced by NLRP3 agonists and then functions as a macroautophagy/autophagy cargo receptor to recognize K63-polyubiquitinated NLRP3 and deliver it to MAP1LC3/LC3-conjugated phagophores for degradation. CCDC50 inhibits the polymerization of NLRP3 and the recruitment of PYCARD/ASC, consequently suppressing the assembly of inflammasomes. ccdc50-knockout mice are more susceptible to dextran-sulfate (DSS)-induced colitis and exhibit more severe gut inflammation with elevated NLRP3 inflammasome activity, suggesting a protective role of CCDC50 in the pathology and progression of inflammatory bowel disease (IBD). Our finding reveals a function of autophagy-related proteins in the regulation of NLRP3-mediated inflammation, thus demonstrating the intricate crosstalk between autophagy and inflammation.
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