{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T19:31:48Z","timestamp":1793302308451,"version":"4.5.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T00:00:00Z","timestamp":1792368000000},"content-version":"vor","delay-in-days":18,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["23K06464"],"award-info":[{"award-number":["23K06464"]}]},{"name":"JSPS KAKENHI","award":["23H05323"],"award-info":[{"award-number":["23H05323"]}]},{"name":"JSPS KAKENHI","award":["23K27635"],"award-info":[{"award-number":["23K27635"]}]},{"name":"JSPS KAKENHI","award":["24K22132"],"award-info":[{"award-number":["24K22132"]}]},{"name":"Research Unit for Advanced Nano-Bioanalysis from Ehime University","id":[{"id":"https:\/\/ror.org\/017hkng22","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cryopyrin-associated periodic syndrome (CAPS) is an autoinflammatory disease caused by gain-of-function mutations in human nucleotide-binding domain, leucine-rich repeat\u2013containing protein 3 (NLRP3), which lead to constitutive inflammasome activation and excessive IL-1\u03b2 secretion. Long-term IL-1 blockade has markedly improved patient outcomes by preventing systemic inflammation and amyloidosis. However, whether chronic NLRP3 mutation exerts inflammasome-independent effects on the cardiac function remains unknown. We generated Nlrp3C257Y\/WT knock-in mice as a novel CAPS model. Long-term survival, systemic inflammation, and cardiac function were assessed by biochemical, histological, and echocardiographic analyses. To determine inflammasome dependency, Nlrp3C257Y\/WT mice were crossed with Asc\u2212\/\u2212 mice to generate double-mutant Nlrp3C257Y\/WT\u2009\u00d7\u2009Asc\u2212\/\u2212 offspring. Nlrp3C257Y\/WT mice exhibited early-onset cutaneous inflammation that gradually subsided, these mice developed marked left ventricular (LV) dilatation and mild systolic dysfunction after approximately 6\u2009mo of age. Histological analysis revealed interstitial myocardial fibrosis in Nlrp3C257Y\/WT mice. This result indicates that Nlrp3C257Y\/WT mutation, which operates as a gain-of-function variant for inflammasome activation, impairs cardiac function largely driven by an inflammasome-dependent mechanism. In contrast, Nlrp3C257Y\/WT\u2009\u00d7\u2009Asc\u2212\/\u2212 mice exhibited marked resolution of systemic inflammation; nevertheless, LV dilatation and reduced fractional shortening persisted. Long-term Nlrp3C257Y\/WT mutation can lead to persistent cardiac dysfunction not only through inflammasome activation but also via inflammasome-independent mechanisms. Our findings reveal previously unrecognized inflammasome-independent mechanisms linking NLRP3 signaling to cardiac dysfunction. This study expands knowledge of the pathophysiological spectrum of CAPS and highlights inflammasome-independent NLRP3 signaling as a potential therapeutic target to prevent chronic cardiac complications in patients with CAPS and NLRP3-associated disorders.<\/jats:p>","DOI":"10.1093\/jimmun\/vkag257","type":"journal-article","created":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T00:02:48Z","timestamp":1792368168000},"source":"Crossref","is-referenced-by-count":0,"title":["Long-term\n                    <i>Nlrp3<\/i>\n                    gain-of-function mutation promotes cardiac dysfunction independent of inflammasome in mice"],"prefix":"10.1093","volume":"215","author":[{"given":"Mie","family":"Kurata","sequence":"first","affiliation":[{"name":"Department of Pathology, Ehime University Proteo-Science Center and Graduate School of Medicine , Ehime,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayo","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine , Ehime,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoe","family":"Kaneko","sequence":"additional","affiliation":[{"name":"Department of Pathology, Ehime University Proteo-Science Center and Graduate School of Medicine , Ehime,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Kameda","sequence":"additional","affiliation":[{"name":"Department of Pathology, Ehime University Proteo-Science Center and Graduate School of Medicine , Ehime,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takanori","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Pathology, Ehime University Proteo-Science Center and Graduate School of Medicine , Ehime,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sho","family":"Hosokawa","sequence":"additional","affiliation":[{"name":"Department of Pathology, Ehime University Proteo-Science Center and Graduate School of Medicine , Ehime,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kasumi","family":"Murakami","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine , Ehime,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Ogura","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Hyogo Medical University , Nishinomiya, Hyogo,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Ishido","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Hyogo Medical University , Nishinomiya, Hyogo,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7461-369X","authenticated-orcid":false,"given":"Osamu","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine , Ehime,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0847-0456","authenticated-orcid":false,"given":"Junya","family":"Masumoto","sequence":"additional","affiliation":[{"name":"Department of Pathology, Ehime University Proteo-Science Center and Graduate School of Medicine , 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