{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T23:07:31Z","timestamp":1789168051103,"version":"build-2803163510"},"reference-count":169,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Sepsis remains a major challenge in critical care medicine worldwide, characterized by a dynamic imbalance of the immune system between two extremes: \u201cimmunoparalysis\u201d and \u201chyperactivation.\u201d This dysregulation severely affects patient survival. The NLRP3 inflammasome, a central molecular platform in innate immunity, has recently been shown to play a critical dual role in the pathogenesis of sepsis. This review systematically outlines the structural features and activation mechanisms of the NLRP3 inflammasome, elaborates on its pro-inflammatory and immunosuppressive effects in sepsis-induced immune dysregulation, and summarizes the associated signaling pathways and regulatory networks. By integrating recent advances in basic and clinical research, we provide an in-depth analysis of the molecular regulatory mechanisms of the NLRP3 inflammasome in sepsis and evaluate its potential as a therapeutic target. Furthermore, this review discusses the opportunities and challenges in translating NLRP3-targeted strategies into clinical practice, emphasizing the potential of precise NLRP3 modulation to restore immune homeostasis in sepsis. Our findings may provide a theoretical foundation and future research directions for developing novel therapeutic approaches.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1751283","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T04:24:09Z","timestamp":1777523049000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The regulatory mechanism of NLRP3 inflammasome in the \u201cimmune paralytic-overactivation\u201d imbalance in sepsis: the latest progress from molecular signaling to clinical translation"],"prefix":"10.3389","volume":"17","author":[{"given":"Gaosheng","family":"Zhou","sequence":"first","affiliation":[{"name":"Critical Care Medicine Laboratory, Yichang Sepsis Clinical Research Center","place":["Yichang, Hubei, China"]},{"name":"Laboratory of Critical Care Medicine, Hubei Provincial Clinical Research Center for Critical Care Medicine (Sepsis Research Collaborative 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