{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T22:47:08Z","timestamp":1793314028294,"version":"4.5.0"},"reference-count":194,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T00:00:00Z","timestamp":1773187200000},"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>Arthritis comprises a spectrum of immune-mediated joint disorders, with rheumatoid arthritis (RA) representing prototypic autoimmunity and psoriatic arthritis (PsA) and ankylosing spondylitis (AS) spanning an autoinflammation\u2013autoimmunity continuum. Across this spectrum, oxidative stress and inflammatory signaling reinforce each other within synovial\/entheseal niches, sustaining immune activation and progressive structural damage. Excess reactive oxygen species (ROS) injure chondrocytes and synoviocytes, activate NF-\u03baB and the NLRP3 inflammasome, and reprogram stromal\u2013immune interactions; inflammatory mediators further increase ROS via NADPH oxidases, mitochondrial dysfunction, and immunometabolic perturbations, sustaining a \u201cROS\u2013inflammation\u2013ROS\u201d loop. Nuclear factor erythroid 2\u2013related factor 2 (Nrf2) is a redox-responsive transcription factor that, upon release from Keap1, drives antioxidant response element\u2013dependent cytoprotective programs. Beyond antioxidation, Nrf2 can dampen NF-\u03baB-linked transcription and modulate ferroptosis, pyroptosis, and autophagy while shaping macrophage and fibroblast-like synoviocyte states. Collectively, these actions position Nrf2 as a context-dependent redox checkpoint that may constrain inflammatory amplification and tune autoimmune-relevant processes (e.g., inflammatory antigen presentation and effector persistence) largely via microenvironmental remodeling rather than direct TCR\/BCR inhibition. Here, we (i) map Nrf2-dependent versus Nrf2-independent nodes in the oxidative stress\u2013inflammation circuit; (ii) compare cell type\u2013 and subtype-specific Nrf2 functions across RA, PsA, and AS; (iii) summarize pharmacologic and natural-product Nrf2 activators together with joint-targeted delivery strategies; and (iv) discuss evidence and gaps for Nrf2 in core autoimmune mechanisms, including self-tolerance, antigen handling, and pathogenic immune memory. This synthesis highlights Nrf2 as a mechanistic bridge between redox balance and immune regulation, informing Nrf2-centered therapies for autoimmune and immune-mediated arthritides.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1775908","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T06:50:25Z","timestamp":1773211825000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Nrf2 as a redox checkpoint in autoimmune joint inflammation: microenvironmental redox control across the arthritis spectrum"],"prefix":"10.3389","volume":"17","author":[{"given":"Mingwang","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Joint Orthopaedics, Gansu Provincial Hospital of Traditional Chinese Medicine","place":["Lanzhou, Gansu, China"]},{"name":"Department of Joint Orthopaedics, First Affiliated Hospital of Gansu University of Traditional Chinese Medicine","place":["Lanzhou, Gansu, China"]},{"name":"Institute of Orthopedics, Gansu Provincial Institute of Traditional Chinese Medicine","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyuan","family":"Gao","sequence":"additional","affiliation":[{"name":"Clinical College of Traditional Chinese Medicine, Gansu University of Traditional Chinese Medicine","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Wang","sequence":"additional","affiliation":[{"name":"The Translational Medicine Research Center, Gansu Provincial Hospital of Traditional Chinese Medicine","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenhua","family":"Shi","sequence":"additional","affiliation":[{"name":"Clinical College of Traditional Chinese Medicine, Gansu University of Traditional Chinese Medicine","place":["Lanzhou, Gansu, 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