{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T11:26:26Z","timestamp":1787052386609,"version":"build-2736575974"},"reference-count":135,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"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>\n                    Acute kidney injury (AKI) is a critical clinical syndrome characterized by a rapid decline in renal function. Dysregulated inflammatory responses play a crucial role in its pathogenesis, contributing to high patient mortality and a tendency to progress to chronic kidney disease (CKD). As a crucial sensor of the innate immune system, the NLRP3 inflammasome participates in the occurrence and development of AKI and its transition to CKD by activating caspase-1, promoting the maturation of IL-1\u03b2\/IL-18, and inducing pyroptosis. This review elucidates the molecular composition of the NLRP3 inflammasome, its canonical and non-canonical activation pathways, and, for the first time, integrates the critical roles of post-translational modifications\u2014including ubiquitination, phosphorylation, acetylation, SUMOylation, and palmitoylation\u2014in regulating its activation, as well as their specific activation mechanisms across distinct subtypes of AKI. The specific mechanisms and pathological significance of the NLRP3 inflammasome in ischemia-reperfusion, sepsis-associated, and contrast-induced AKI were analyzed. Furthermore, we summarize current interventional strategies targeting the NLRP3 inflammasome and its upstream\/downstream molecules, including direct inhibitors, mitophagy inducers, K\n                    <jats:sup>+<\/jats:sup>\n                    channel modulators, caspase-1 inhibitors, and indirect inhibitor-based agents. Moreover, we assess their protective effects in AKI animal models and the bottlenecks in clinical translation. Finally, future research directions are proposed, such as cell type-specific functional analysis, dynamic regulation of post-translational modifications, and combined targeted therapy for the long-term transition of AKI to CKD, aiming to provide a theoretical basis and novel ideas for the precise therapy of AKI.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1924802","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T10:34:34Z","timestamp":1787049274000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["NLRP3 inflammasome in acute kidney injury: molecular mechanisms, post-translational regulation, and immunotherapeutic potential"],"prefix":"10.3389","volume":"17","author":[{"given":"Mingru","family":"Ma","sequence":"first","affiliation":[{"name":"Inner Mongolia Key Laboratory for Pathogenesis and Diagnosis of Rheumatic and Autoimmune Diseases, The Affiliated Hospital of Inner Mongolia Medical University","place":["Hohhot, China"]},{"name":"The State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Science, Inner Mongolia University","place":["Hohhot, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manling","family":"Zhang","sequence":"additional","affiliation":[{"name":"Inner Mongolia Key Laboratory for Pathogenesis and Diagnosis of Rheumatic and Autoimmune Diseases, The Affiliated Hospital of Inner Mongolia Medical University","place":["Hohhot, China"]},{"name":"Department of Rheumatology and Immunology, The Affiliated Hospital of Inner Mongolia Medical University","place":["Hohhot, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongfei","family":"Sun","sequence":"additional","affiliation":[{"name":"Inner Mongolia Key Laboratory for Pathogenesis and Diagnosis of Rheumatic and Autoimmune Diseases, The Affiliated Hospital of Inner Mongolia Medical University","place":["Hohhot, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinran","family":"Xie","sequence":"additional","affiliation":[{"name":"School of Basic Medicine Sciences, Inner Mongolia Medical University","place":["Hohhot, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xudong","family":"Guo","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Science, Inner Mongolia University","place":["Hohhot, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongbin","family":"Li","sequence":"additional","affiliation":[{"name":"Inner Mongolia Key Laboratory for Pathogenesis and Diagnosis of Rheumatic and Autoimmune Diseases, The Affiliated Hospital of Inner Mongolia Medical University","place":["Hohhot, China"]},{"name":"Department of Rheumatology and Immunology, The Affiliated Hospital of Inner Mongolia Medical 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