Marshall Courtney Lynn, Hemshekhar Mahadevappa, Mookherjee Neeloffer, O'Neil Liam J
Department of Immunology, University of Manitoba, Winnipeg, MB, Canada.
Manitoba Centre for Proteomics and Systems Biology, Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada.
Front Immunol. 2025 May 20;16:1588419. doi: 10.3389/fimmu.2025.1588419. eCollection 2025.
Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease characterized by joint inflammation and damage, leading to disability and pain. The etiology of RA is undefined but considered multifactorial, as interactions between genetics and environmental factors lead to the generation of autoantibodies that target synovial joints. Smoking is a well-established and widely studied risk factor for RA development and is associated with a reduced response to treatments and poor clinical outcomes. Murine models of inflammatory arthritis have provided many insights into the pathogenesis of RA and have recently been used to explore the relationship between cigarette smoking and RA. In this review, we comprehensively appraise the current literature investigating cigarette smoke exposure in murine models of inflammatory arthritis, focused on RA. The current literature indicates that the influence of smoke exposure on molecular and disease outcomes depends on the timepoint of exposure and genetic background of the mice. Further, dose-dependent increases in disease manifestations reproduce human clinical data that the intensity of smoking is linked to disease but demosntrate that there may be a plateau effect. Finally, we consolidate mechanistic findings to describe a potential mechanism through which cigarette smoke exacerbates murine arthritis. Understanding how these factors, genetics, timing, and intensity of exposure modulate response to CS in inflammatory arthritis models may lead to better drug development and personalized treatment strategies, ultimately improving outcomes for RA patients with a smoking history.
类风湿性关节炎（RA）是一种慢性自身免疫性炎症疾病，其特征为关节炎症和损伤，可导致残疾和疼痛。RA的病因尚不明确，但被认为是多因素的，因为遗传因素与环境因素之间的相互作用会导致产生靶向滑膜关节的自身抗体。吸烟是RA发病的一个已被充分证实且广泛研究的风险因素，并且与治疗反应降低及临床预后不良相关。炎症性关节炎的小鼠模型为RA的发病机制提供了许多见解，最近还被用于探究吸烟与RA之间的关系。在本综述中，我们全面评估了当前关于炎症性关节炎小鼠模型（重点是RA）中香烟烟雾暴露的文献。当前文献表明，烟雾暴露对分子和疾病结局的影响取决于暴露时间点和小鼠的遗传背景。此外，疾病表现的剂量依赖性增加再现了人类临床数据，即吸烟强度与疾病相关，但表明可能存在平台效应。最后，我们整合了机制研究结果，以描述香烟烟雾加重小鼠关节炎的潜在机制。了解这些因素（遗传学、暴露时间和强度）如何调节炎症性关节炎模型中对香烟烟雾的反应，可能会带来更好的药物开发和个性化治疗策略，最终改善有吸烟史的RA患者的预后。
