{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:16:37Z","timestamp":1791299797895,"version":"4.1.0"},"reference-count":53,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>The NOD\u2010like receptor protein 3 (NLRP3) inflammasome is a central contributor to human acute and chronic liver disease, yet the molecular and cellular mechanisms by which its activation precipitates injury remain incompletely understood. Here, we present single cell transcriptomic profiling of livers from a global transgenic tamoxifen\u2010inducible constitutively activated <jats:italic toggle=\"yes\">Nlrp3<\/jats:italic>\n                                 <jats:sup>A350V<\/jats:sup> mutant mouse, and we investigate the changes in parenchymal and nonparenchymal liver cell gene expression that accompany inflammation and fibrosis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>Our results demonstrate that NLRP3 activation causes chronic extramedullary myelopoiesis marked by myeloid progenitors that differentiate into proinflammatory neutrophils, monocytes, and monocyte\u2010derived macrophages. We observed prominent neutrophil infiltrates with increased Ly6g<jats:sup>HI<\/jats:sup> and Ly6g<jats:sup>INT<\/jats:sup> cells exhibiting transcriptomic signatures of granulopoiesis typically found in the bone marrow. This was accompanied by a marked increase in Ly6c<jats:sup>HI<\/jats:sup> monocytes differentiating into monocyte\u2010derived macrophages that express transcriptional programs similar to macrophages of NASH models. NLRP3 activation also down\u2010regulated metabolic pathways in hepatocytes and shifted hepatic stellate cells toward an activated profibrotic state based on expression of collagen and extracellular matrix regulatory genes.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>These results define the single cell transcriptomes underlying hepatic inflammation and fibrosis precipitated by NLRP3 activation. Clinically, our data support the notion that NLRP3\u2010induced mechanisms should be explored as therapeutic target in NASH\u2010like inflammation.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.32320","type":"journal-article","created":{"date-parts":[[2022,1,8]],"date-time":"2022-01-08T13:49:57Z","timestamp":1641649797000},"page":"727-741","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":57,"title":["NOD\u2010like receptor protein 3 activation causes spontaneous inflammation and fibrosis that mimics human NASH"],"prefix":"10.1097","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7022-9220","authenticated-orcid":false,"given":"David M.","family":"Calcagno","sequence":"first","affiliation":[{"name":"Department of Bioengineering,University of California San Diego,San 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