What is it about?
The negative feedback system that tempers inflammasome activation and downstream inflammation remains unknown. To date, there has been intensive study of the role of Gasdermin D as a central player in executing pyroptosis, the cell death pathway downstream of inflammasome activation. In this study, we unexpectedly found that the N-terminal fragment of Gasdermin D can also directly target and inhibit caspase-1/11, the effector caspases in inflammasome pathways, and so suppress downstream triggering of inflammation.
Featured Image
Photo by Patrick Perkins on Unsplash
Why is it important?
In the long-term evolution of the immune system, negative feedback regulatory mechanisms have been developed to control excessive inflammatory response. At present, many studies have reported a wide range of negative feedback mechanisms involved in the regulation of the inflammatory pathway. Here, we for the first time described a negative feedback regulatory mechanism in which the cleaved N-terminal fragment of GSDMD can inhibit caspase-1/11 activity after inflammasome activation.
Perspectives
Our findings indicate the dualist pro- and antiinflammatory effects of the N-terminal fragment of GSDMD can help the body dynamically regulate inflammation and provide that yin-yang balance in immune system to avoid pathological consequences of excessive and uncontrolled inflammation. So I hope this article can bring new inspiration to the research on inflammation regulation in the field.
Shuo Yang
Read the Original
This page is a summary of: The Gasdermin D N-terminal fragment acts as a negative feedback system to inhibit inflammasome-mediated activation of Caspase-1/11, Proceedings of the National Academy of Sciences, November 2022, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2210809119.
You can read the full text:
Resources
Contributors
The following have contributed to this page
