文献类型：期刊文献

英文题名：Nrf2 as a redox checkpoint in autoimmune joint inflammation: microenvironmental redox control across the arthritis spectrum

作者：Zhou, Mingwang[1,2,3];Gao, Haiyuan[4];Wang, Xiaoping[5];Shi, Zhenhua[4];Yang, Xing[4];Li, YuNan[4];Li, XinHao[4];Zhao, Yongqiang[6]

第一作者：Zhou, Mingwang

通信作者：Zhou, MW[1];Zhou, MW[2];Zhou, MW[3];Zhao, YQ[4]

机构：[1]Gansu Prov Hosp Tradit Chinese Med, Dept Joint Orthopaed, Lanzhou, Gansu, Peoples R China;[2]Gansu Univ Tradit Chinese Med, Affiliated Hosp 1, Dept Joint Orthopaed, Lanzhou, Gansu, Peoples R China;[3]Gansu Prov Inst Tradit Chinese Med, Inst Orthoped, Lanzhou, Gansu, Peoples R China;[4]Gansu Univ Tradit Chinese Med, Clin Coll Tradit Chinese Med, Lanzhou, Gansu, Peoples R China;[5]Gansu Prov Hosp Tradit Chinese Med, Translat Med Res Ctr, Lanzhou, Gansu, Peoples R China;[6]Gansu Prov Hosp Tradit Chinese Med, Urol, Lanzhou, Gansu, Peoples R China

第一机构：Gansu Prov Hosp Tradit Chinese Med, Dept Joint Orthopaed, Lanzhou, Gansu, Peoples R China

通信机构：[1]corresponding author), Gansu Prov Hosp Tradit Chinese Med, Dept Joint Orthopaed, Lanzhou, Gansu, Peoples R China;[2]corresponding author), Gansu Univ Tradit Chinese Med, Affiliated Hosp 1, Dept Joint Orthopaed, Lanzhou, Gansu, Peoples R China;[3]corresponding author), Gansu Prov Inst Tradit Chinese Med, Inst Orthoped, Lanzhou, Gansu, Peoples R China;[4]corresponding author), Gansu Prov Hosp Tradit Chinese Med, Urol, Lanzhou, Gansu, Peoples R China.|[10735]甘肃中医药大学;

年份：2026

卷号：17

外文期刊名：FRONTIERS IN IMMUNOLOGY

收录：;Scopus(收录号：2-s2.0-105033674330);WOS:【SCI-EXPANDED(收录号:WOS:001722372500001)】；

基金：The author(s) declared that financial support was received for this work and/or its publication. This work was supported by the Central Guidance Science and Technology Development Fund Project (24ZYQA037), Gansu Provincial Clinical Research Center for Bone and Joint Degenerative Diseases (18JR2FA009), and Key R&D Program of Gansu Province -Social Development Projects (25YF7FA059, 22YF7FA103).

语种：英文

外文关键词：arthritis; autoimmune synovitis; autoimmunity; inflammation; Nrf2; oxidative stress; reactive oxygen species

摘要：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-autoimmunity 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-kappa B and the NLRP3 inflammasome, and reprogram stromal-immune interactions; inflammatory mediators further increase ROS via NADPH oxidases, mitochondrial dysfunction, and immunometabolic perturbations, sustaining a "ROS-inflammation-ROS" loop. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a redox-responsive transcription factor that, upon release from Keap1, drives antioxidant response element-dependent cytoprotective programs. Beyond antioxidation, Nrf2 can dampen NF-kappa B-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-inflammation circuit; (ii) compare cell type- 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.