The incidence of rheumatoid arthritis is correlated with age. In this study, we analyzed the association of the incidence and severity of glucose-6-phosphate isomerase (G6PI)-induced arthritis with age in two different mouse strains. Young and very old mice from two different arthritis-susceptible wild-type mouse strains were analyzed after a single subcutaneous injection of G6PI s.c. The metabolism and the function of synoviocytes were analyzed in vitro, the production of bioactive lipid mediators by myeloid cells and synoviocytes was assessed in vitro and ex vivo by UPLC-MS-MS, and flow cytometry was used to verify age-related changes of immune cell composition and function. While the severity of arthritis was independent from age, the onset was delayed in old mice. Old mice showed common signs of immune aging like thymic atrophy associated with decreased CD4+ effector T cell numbers. Despite its decrease, the effector T helper (Th) cell compartment in old mice was reactive and functionally intact, and their Tregs exhibited unaltered suppressive capacities. In homeostasis, macrophages and synoviocytes from old mice produced higher amounts of pro-inflammatory cyclooxygenase (COX)-derived products. However, this functional difference did not remain upon challenge in vitro nor upon arthritis reactions ex vivo. While old mice show a higher baseline of inflammatory functions, this does not result in increased reaction towards self-antigens in arthritis-susceptible mouse strains. Together, our data from two different mouse strains show that the susceptibility for G6PI-induced arthritis is not age-dependent.

中文翻译：

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G6PI 诱导的关节炎的发生率和严重程度在基因不同的小鼠品系中不会随着年龄的增长而增加

类风湿性关节炎的发病率与年龄有关。在这项研究中，我们分析了两种不同小鼠品系中葡萄糖 6-磷酸异构酶 (G6PI) 诱导的关节炎的发生率和严重程度与年龄的关联。单次皮下注射 G6PI sc 后分析了来自两种不同的关节炎易感野生型小鼠品系的年轻和非常年老的小鼠 体外分析了滑膜细胞的代谢和功能，骨髓细胞和滑膜细胞产生的生物活性脂质介质是通过 UPLC-MS-MS 进行体外和离体评估，并使用流式细胞术验证免疫细胞组成和功能的年龄相关变化。虽然关节炎的严重程度与年龄无关，但老年小鼠的发病时间有所延迟。老年小鼠表现出免疫衰老的常见迹象，如与 CD4+ 效应 T 细胞数量减少相关的胸腺萎缩。尽管其减少，老年小鼠的效应 T 辅助 (Th) 细胞室是反应性的且功能完整，并且它们的 Treg 表现出未改变的抑制能力。在体内平衡中，来自老年小鼠的巨噬细胞和滑膜细胞产生了更多的促炎环氧合酶 (COX) 衍生产物。然而，这种功能差异在体外激发和离体关节炎反应时均不存在。虽然老年小鼠显示出更高的炎症功能基线，但这并不会导致对关节炎易感小鼠品系的自身抗原的反应增加。总之，我们来自两种不同小鼠品系的数据表明 G6PI 诱导的关节炎的易感性与年龄无关。