Galligan Carole L, Fish Eleanor N
1 Division of Advanced Diagnostics, Toronto General Hospital Research Institute, University Health Network , Toronto, Canada .
2 Department of Immunology, University of Toronto , Toronto, Canada .
J Interferon Cytokine Res. 2017 Oct;37(10):440-448. doi: 10.1089/jir.2017.0063. Epub 2017 Oct 3.
Rheumatoid arthritis (RA) is a systemic autoimmune disease affecting multiple joints. It remains unclear which factors in the circulation are associated with the systemic spread of the disease. Fibrocytes are pluripotent mesenchymal stem cells present in the circulation of RA patients. Our earlier findings implicated activated fibrocytes in the etiology of onset and pathogenesis of RA. Elevated levels of interleukin-34 (IL-34) in the serum and synovial fluid of RA patients are associated with rheumatoid factor and anticyclic citrullinated peptide antibodies, indicators of RA. Moreover, IL-34 levels are independent predictors of radiographic progression in RA patients. We provide evidence of simultaneous elevated levels of IL-34 and increased numbers of activated fibrocytes in the circulation of mice induced to develop arthritis. In vitro, IL-34 treatment induced the proliferation of fibrocytes, mediated by activation of cognate CSF-R1s on fibrocytes. Taken together, we infer that IL-34 has a role in stimulating fibrocyte proliferation and activation during arthritis, thereby contributing to both onset of RA and systemic spread of disease.
类风湿性关节炎（RA）是一种影响多个关节的全身性自身免疫性疾病。目前尚不清楚循环系统中的哪些因素与该疾病的全身扩散有关。纤维细胞是存在于RA患者循环系统中的多能间充质干细胞。我们早期的研究结果表明，活化的纤维细胞与RA的发病机制和病因有关。RA患者血清和滑液中白细胞介素-34（IL-34）水平升高与类风湿因子和抗环瓜氨酸肽抗体相关，这些都是RA的指标。此外，IL-34水平是RA患者影像学进展的独立预测指标。我们提供的证据表明，在诱导发生关节炎的小鼠循环系统中，IL-34水平同时升高，活化纤维细胞数量增加。在体外，IL-34处理通过激活纤维细胞上的同源CSF-R1介导纤维细胞增殖。综上所述，我们推断IL-34在关节炎期间刺激纤维细胞增殖和活化，从而导致RA的发病和疾病的全身扩散。
