{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Xiao J"],"funding":["National Institute of Arthritis and Musculoskeletal and Skin Diseases","NIAMS NIH HHS","Shriners Hospitals for Children"],"pagination":["e3000047"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6235378"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["16(11)"],"pubmed_abstract":["Mutated NLRP3 assembles a hyperactive inflammasome, which causes excessive secretion of interleukin (IL)-1β and IL-18 and, ultimately, a spectrum of autoinflammatory disorders known as cryopyrinopathies of which neonatal-onset multisystem inflammatory disease (NOMID) is the most severe phenotype. NOMID mice phenocopy several features of the human disease as they develop severe systemic inflammation driven by IL-1β and IL-18 overproduction associated with damage to multiple organs, including spleen, skin, liver, and skeleton. Secretion of IL-1β and IL-18 requires gasdermin D (GSDMD), which-upon activation by the inflammasomes-translocates to the plasma membrane where it forms pores through which these cytokines are released. However, excessive pore formation resulting from sustained activation of GSDMD compromises membrane integrity and ultimately causes a pro-inflammatory form of cell death, termed pyroptosis. In this study, we first established a strong correlation between NLRP3 inflammasome activation and GSDMD processing and pyroptosis in vitro. Next, we used NOMID mice to determine the extent to which GSDMD-driven pyroptosis influences the pathogenesis of this disorder. Remarkably, all NOMID-associated inflammatory symptoms are prevented upon ablation of GSDMD. Thus, GSDMD-dependent actions are required for the pathogenesis of NOMID in mice."],"journal":["PLoS biology"],"pubmed_title":["Gasdermin D mediates the pathogenesis of neonatal-onset multisystem inflammatory disease in mice."],"pmcid":["PMC6235378"],"funding_grant_id":["R01 AR049192","AR068972","R01 AR068972","AR049192","R01 AR072623","R01 AR064755","AR054326","AR064755","AR072623"],"pubmed_authors":["Civitelli R","Link DC","Kress D","Kanneganti TD","Xiao J","Wang C","Alippe Y","Xu C","Yao JC","Mbalaviele G","Abu-Amer Y"],"additional_accession":[]},"is_claimable":false,"name":"Gasdermin D mediates the pathogenesis of neonatal-onset multisystem inflammatory disease in mice.","description":"Mutated NLRP3 assembles a hyperactive inflammasome, which causes excessive secretion of interleukin (IL)-1β and IL-18 and, ultimately, a spectrum of autoinflammatory disorders known as cryopyrinopathies of which neonatal-onset multisystem inflammatory disease (NOMID) is the most severe phenotype. NOMID mice phenocopy several features of the human disease as they develop severe systemic inflammation driven by IL-1β and IL-18 overproduction associated with damage to multiple organs, including spleen, skin, liver, and skeleton. Secretion of IL-1β and IL-18 requires gasdermin D (GSDMD), which-upon activation by the inflammasomes-translocates to the plasma membrane where it forms pores through which these cytokines are released. However, excessive pore formation resulting from sustained activation of GSDMD compromises membrane integrity and ultimately causes a pro-inflammatory form of cell death, termed pyroptosis. In this study, we first established a strong correlation between NLRP3 inflammasome activation and GSDMD processing and pyroptosis in vitro. Next, we used NOMID mice to determine the extent to which GSDMD-driven pyroptosis influences the pathogenesis of this disorder. Remarkably, all NOMID-associated inflammatory symptoms are prevented upon ablation of GSDMD. Thus, GSDMD-dependent actions are required for the pathogenesis of NOMID in mice.","dates":{"release":"2018-01-01T00:00:00Z","publication":"2018 Nov","modification":"2024-11-09T22:56:40.313Z","creation":"2019-03-27T00:10:29Z"},"accession":"S-EPMC6235378","cross_references":{"pubmed":["30388107"],"doi":["10.1371/journal.pbio.3000047"]}}