An unexpected path for inflammasome-mediated inflammation

Many inflammatory disorders are linked to an overactive NLRP3 inflammasome due to increased cell death and production of inflammatory cytokines.  In some cases, targeting the pyroptosis (an inflammatory form of cell death) pore forming unit GSDMD alleviates these disorders, but the direct role of GSDMD during sustained NLRP3 inflammasome activation is unclear. Using various knockout mouse models, Wang et al. determined that constitutive NLRP3 activation was able to still induce inflammation in the absence of GSDMD seemingly through GSDME-mediated pyroptosis. Importantly, NLRP3 overactivation associated pathologies could be inhibited by pharmacologically targeting both GSDMD and GSDME activation with CuET.  Thus, this work presents a potential treatment for inflammatory disorders caused by sustained NLRP3 inflammasome activation.

Read the full study published in the October 22, 2021 issue of Science Immunology here.