AA467197 controls the hyperactivation of the NLRP3 inflammasome during infection

Qiannv Liu; Weitao Li; Yan Qian; Chunlei Wang; Pengyan Xia

doi:10.59717/j.xinn-life.2023.100012

The Innovation Life > 2023 Vol. 1 > No. 1 > 100012

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AA467197 controls the hyperactivation of the NLRP3 inflammasome during infection

1.
Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing 100191, China
2.
NHC Key Laboratory of Medical Immunology, Peking University, Beijing 100191, China
3.
Key Laboratory of Molecular Immunology, Chinese Academy of Medical Sciences, Beijing 100191, China

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Corresponding author: xiap@pku.edu.cn
Received Date: 12 March 2023

Accepted Date: 10 May 2023

Published Online: 28 May 2023

The Innovation Life 1(1), https://doi.org/10.59717/j.xinn-life.2023.100012 | Cite this article

GRAPHICAL ABSTRACT

GRAPHICAL ABSTRACT

PUBLIC SUMMARY

PUBLIC SUMMARY
1. Protein AA467197 is an essential regulator in chronic infections.
  
  AA467197 is positively involved in the establishment of hyperactivated NLRP3 inflammasome.
  
  AA467197 binds to GSDMD to limit its cleavage and allows persistent IL-1β secretion and cell viability.
  
  AA467197 deficiency exacerbates immune responses.

ABSTRACT

ABSTRACT

The hyperactivation of NLRP3 plays an essential role during infections, in which case a small portion of GSDMD is processed to become active and IL-1β is secreted for a long duration. However, the mechanism underlying NLRP3 hyperactivation remains unclear. Here we took use of the CRISPR/Cas9 technology to screen for genes involved in NLRP3 hyperactivation. We discovered that AA467197 suppresses the NLRP3 inflammasome to a hyperactivation state, and without affecting the canonical NLRP3 inflammasome activation. During infections caused by low doses of pathogens, AA467197 deficient cells have elevated rates of cell death compared with wild-type controls. Mechanistically, AA467197 binds to GSDMD and hinders its processing by the oligomerized caspase-1. Cells deficient for AA467197 undergo canonical NLRP3 inflammasome activation when encountering low-dose infections, leading to severe GSDMD cleavage and cell pyroptosis. Our results uncover a molecular mechanism for the exquisite regulation of the NLRP3 inflammasome in a hyperactivated state, which might be useful for further clinical treatment of infections.

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Liu Q., Li W., Qian Y., et al., (2023). AA467197 controls the hyperactivation of the NLRP3 inflammasome during infection. The Innovation Life 1(1), 100012. https://doi.org/10.59717/j.xinn-life.2023.100012

Liu Q., Li W., Qian Y., et al., (2023). AA467197 controls the hyperactivation of the NLRP3 inflammasome during infection. The Innovation Life 1(1), 100012. https://doi.org/10.59717/j.xinn-life.2023.100012

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AA467197 controls the hyperactivation of the NLRP3 inflammasome during infection

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