{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T16:21:10Z","timestamp":1791649270173,"version":"4.3.4"},"reference-count":58,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,6,11]],"date-time":"2023-06-11T00:00:00Z","timestamp":1686441600000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071790"],"award-info":[{"award-number":["82071790"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82070415"],"award-info":[{"award-number":["82070415"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271797"],"award-info":[{"award-number":["82271797"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MedComm"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Epigenetic regulation of inflammatory macrophages governs inflammation initiation and resolution in the pathogenesis of rheumatoid arthritis (RA). Nevertheless, the mechanisms underlying macrophage\u2010mediated arthritis injuries remain largely obscure. Here, we found that increased expression of lysine acetyltransferase 2A (KAT2A) in synovial tissues was closely correlated with inflammatory joint immunopathology in both RA patients and experimental arthritis mice. Administration of MB\u20103, the KAT2A\u2010specific chemical inhibitor, significantly ameliorated the synovitis and bone destruction in collagen\u2010induced arthritis model. Both pharmacological inhibition and siRNA silencing of KAT2A, not only suppressed innate stimuli\u2010triggered proinflammatory gene (such as\n                    <jats:italic>Il1b<\/jats:italic>\n                    and\n                    <jats:italic>Nlrp3<\/jats:italic>\n                    ) transcription but also impaired NLR family pyrin domain containing 3 (NLRP3) inflammasome activation in vivo and in vitro. Mechanistically, KAT2A facilitated macrophage glycolysis reprogramming through suppressing nuclear factor\u2010erythroid 2\u2010related factor 2 (NRF2) activity as well as downstream antioxidant molecules, which supported histone 3 lysine 9 acetylation (H3K9ac) and limited NRF2\u2010mediated transcriptional repression of proinflammatory genes. Our study proves that acetyltransferase KAT2A licenses metabolic and epigenetic reprogramming for NLRP3 inflammasome activation in inflammatory macrophages, thereby targeting KAT2A represents a potential therapeutic approach for patients suffering from RA and relevant inflammatory diseases.\n                  <\/jats:p>","DOI":"10.1002\/mco2.306","type":"journal-article","created":{"date-parts":[[2023,6,12]],"date-time":"2023-06-12T01:55:34Z","timestamp":1686534934000},"source":"Crossref","is-referenced-by-count":51,"title":["Targeting KAT2A inhibits inflammatory macrophage activation and rheumatoid arthritis through epigenetic and metabolic reprogramming"],"prefix":"10.1002","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4932-6270","authenticated-orcid":false,"given":"Yunkai","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pathogen Biology Naval Medical University  Shanghai China"},{"name":"National Key Laboratory of Immunity &amp; 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