X-HiDE publication on NLRP3 activation

We are happy to share our latest paper, in which we present a detailed model of the NLRP3 inflammasome activation and a hypothesis for a common activation mechanism on which various inflammasome trigger signals may converge:

The NLRP3 inflammasome is a key regulator of inflammation. In the context of infection (priming & licensing), it reacts to danger signals (activation) that appears to reflect compromised internal membranes. NLRP3 is an essential component of the cellular defence against infection, but improper activation – e.g. through genetic changes – can lead to autoinflammatory diseases.

In this study, we create a detailed molecular model of the NLRP3 inflammasome activation based on an in-depth literature review. The goal is to provide a better understanding of this system and a knowledge scaffold to analyse, interpret, and understand how perturbations and genetic changes combine to affect the function of this system. Focussing on the areas that are sufficiently well known, we compile molecular level knowledge on priming, licensing, and activation of the NLRP3 inflammasome into a mechanistic model, and we find that the existing knowledge is sufficient to qualitatively explain activation and the need for priming & licensing. Moreover, our study indicates that seemingly diverse stimuli triggering NLRP3 converges on a single common activation mechanism.