Monocytes’ plasticity has an important role in the development of rheumatoid arthritis (RA), an autoimmune disease exhibiting greater prevalence in women. Contribution of this phenomenon to sex bias in RA severity was investigated in rat collagen-induced arthritis (CIA) model of RA. The greater severity of CIA in females (exhibiting signs of bone resorption) was accompanied by the higher blood level of advanced oxidation protein products and a more pro-oxidant profile. Consistently, in females, the greater density of giant multinuclear cells (monocytes/macrophages and osteoclasts) in inflamed joint tissue was found. This correlated with the higher frequencies of CCR2- and CX3CR1- expressing cells (precursors of inflammatory monocytes/macrophages and osteoclasts) among CD11b+ splenocytes. This in conjunction with the enhanced migratory capacity of CD11b+ monocytic cells in females compared with males could be linked with the higher frequencies of CCR2+CX3CR1-CD43^lowCD11b+ and CCR2-CX3CR1+CD43^hiCD11b+ cells (corresponding to “classical” and “non-classical” monocytes, respectively) and the greater density of CD68+ cells (monocytes/macrophages and osteoclast precursors/osteoclasts) in blood and inflamed paws from female rats, respectively. Consistently, the higher levels of GM-CSF, TNF-α and IL-6, IL-1β (driving Th17 cell differentiation), and IL-17 followed by the lower level of IL-10 were measured in inflamed paw cultures from female compared with male rats. To the greater IL-17 production (associated with enhanced monocyte immigration and differentiation into osteoclasts) most likely contributed augmented Th17 cell generation in the lymph nodes draining arthritic joints from female compared with male rats. Overall, the study suggests the sex-specific contribution of monocytic lineage cells to CIA, and possibly RA development.

单核细胞的可塑性在类风湿性关节炎 (RA) 的发展中具有重要作用，这是一种在女性中发病率更高的自身免疫性疾病。在 RA 的大鼠胶原诱导的关节炎 (CIA) 模型中研究了这种现象对 RA 严重程度的性别偏见的贡献。女性中 CIA 的严重程度（表现出骨吸收的迹象）伴随着更高的血液高级氧化蛋白产物水平和更多的促氧化特征。一致地，在女性中，在发炎的关节组织中发现了更高密度的巨大多核细胞（单核细胞/巨噬细胞和破骨细胞）。这与 CD11b+ 脾细胞中 CCR2 和 CX3CR1 表达细胞（炎性单核细胞/巨噬细胞和破骨细胞的前体）的较高频率相关。^低CD11b+ 和 CCR2-CX3CR1+CD43^高CD11b+ 细胞（分别对应于“经典”和“非经典”单核细胞）和较高密度的 CD68+ 细胞（单核细胞/巨噬细胞和破骨细胞前体/破骨细胞）分别来自雌性大鼠的血液和发炎的爪子。一致地，在来自女性的发炎爪培养物中测量到较高水平的 GM-CSF、TNF-α 和 IL-6、IL-1β（驱动 Th17 细胞分化）和 IL-17，随后是较低水平的 IL-10。与雄性大鼠。与雄性大鼠相比，更大的 IL-17 产生（与增强的单核细胞迁移和向破骨细胞的分化相关）很可能有助于增加从雌性大鼠关节炎关节引流的淋巴结中的 Th17 细胞生成。总体而言，该研究表明单核细胞谱系细胞对 CIA 和可能的 RA 发展的性别特异性贡献。