{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T06:04:26Z","timestamp":1780380266949,"version":"3.54.1"},"reference-count":128,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"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                    Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation, joint destruction, and systemic comorbidities, particularly cardiovascular disease (CVD) associated with severe dyslipidemia. The bidirectional crosstalk between immune-inflammatory processes and lipid metabolic disturbances is increasingly recognized as a key driver of RA pathogenesis, yet the molecular mechanisms integrating these domains remain poorly understood. This review synthesizes current evidence to propose the Sirtuin 1 (SIRT1)\/signal transducer and activator of transcription 3 (STAT3) axis as a central regulator of immune, inflammatory, and lipid metabolic dysregulation in RA. SIRT1, an NAD\n                    <jats:sup>+<\/jats:sup>\n                    -dependent deacetylase, functions as a metabolic sensor with anti-inflammatory and lipid-regulating properties, whereas STAT3 acts as a proinflammatory transcription factor driving Th17 differentiation, synovial hyperplasia, and metabolic reprogramming. SIRT1 directly deacetylates and inactivates STAT3, establishing an antagonistic yin\u2013yang relationship. In RA, chronic inflammation and metabolic stress suppress SIRT1 and hyperactivate STAT3, creating a positive feedback loop that perpetuates immune imbalance and lipid dysfunction. We further discuss therapeutic strategies targeting this axis, including SIRT1 activators, STAT3 inhibitors, and dietary interventions such as\n                    <jats:italic>n<\/jats:italic>\n                    -3 polyunsaturated fatty acids, which hold promise for simultaneously mitigating inflammation and correcting metabolic abnormalities in RA. This integrated perspective challenges the traditional siloed approach and opens new avenues for immunometabolic therapy in RA.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1746043","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T05:41:34Z","timestamp":1780378894000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The SIRT1\/STAT3 axis as a central regulator of immune, inflammatory, and lipid metabolic dysregulation in rheumatoid arthritis: therapeutic implications"],"prefix":"10.3389","volume":"17","author":[{"given":"Chengzhi","family":"Cong","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology, First Affiliated Hospital of Anhui University of Chinese Medicine","place":["Hefei, Anhui, China"]},{"name":"First Clinical Medical School, Anhui University of Chinese Medicine","place":["Hefei, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, First Affiliated Hospital of Anhui University of Chinese Medicine","place":["Hefei, Anhui, China"]},{"name":"Anhui Provincial Key Laboratory for Applied Basic and Clinical Translational Research on Rheumatologic Diseases in Traditional Chinese Medicine, Anhui Academy of Chinese Medicine","place":["Hefei, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, First Affiliated Hospital of Anhui University of Chinese Medicine","place":["Hefei, Anhui, China"]},{"name":"Anhui Provincial Key Laboratory for Applied Basic and Clinical Translational Research on Rheumatologic Diseases in Traditional Chinese Medicine, Anhui Academy of Chinese Medicine","place":["Hefei, Anhui, 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