Department of Medical Records and Health Information Management, College of Nursing and Health, Kongju National University, 56 Kongjudaehakro, Kongju, Chungnam, 314-701, Republic of Korea.
Molecular Recognition Research Center, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea; Division of Bio-Medical Science & Technology, KIST-School, Korea University of Science and Technology (UST), Seoul, 02792, Republic of Korea.
Mol Immunol. 2021 Jul;135:84-94. doi: 10.1016/j.molimm.2021.04.008. Epub 2021 Apr 17.
The immune system plays a critical role not only in homeostasis of the body but also in pathogenesis. Autoimmunity and dysregulation of the immune balance are closely related to age. To examine the influence of age on autoimmunity, the pathophysiological features of experimental autoimmune encephalomyelitis (EAE) induced at different ages were elucidated on the basis of plasma-level metabolic changes. In the present study, female 6 week-old (6 W) and 15 month-old (15 M) C57BL/6 mice were immunized for EAE induction. The plasma and tissue samples were collected to determine the phenotypic characteristics. The activity of NADPH oxidase in plasma and the IL-6 concentrations in the brain and spinal cord were higher in both EAE groups compared to those in the control groups as well as in the 15 M EAE (15 M-E) group compared to those in the 6 W EAE (6 W-E) group. The metabolomic profiles related to characteristics of EAE were characterized by the biosynthesis of unsaturated fatty acids and the metabolism of tryptophan, tyrosine and sphingolipid. The reduced availability of unsaturated fatty acids and perturbations in tryptophan metabolism were high risk factors for EAE development regardless of age. The changes in tyrosine metabolism and sphingolipid metabolites were more dramatic in the 15 M-E group. From these findings, it can be concluded that changes in unsaturated fatty acid and tryptophan metabolism contributed to the development of EAE, whereas changes in sphingolipid and tyrosine metabolism, which corresponded to age, were additional risk factors that influenced the incidence and severity of EAE.
免疫系统不仅在维持身体内环境稳定方面发挥着关键作用，而且在发病机制中也起着关键作用。自身免疫和免疫平衡失调与年龄密切相关。为了研究年龄对自身免疫的影响，本研究基于血浆代谢变化，阐明了不同年龄诱导实验性自身免疫性脑脊髓炎（EAE）的病理生理特征。在本研究中，雌性 6 周龄（6W）和 15 月龄（15M）C57BL/6 小鼠被免疫以诱导 EAE。收集血浆和组织样本以确定表型特征。与对照组相比，两组 EAE 组（6W-E 和 15M-E）的血浆 NADPH 氧化酶活性和大脑及脊髓中的 IL-6 浓度均升高，且 15M-E 组高于 6W-E 组。与 EAE 特征相关的代谢组学图谱由不饱和脂肪酸的生物合成和色氨酸、酪氨酸和鞘脂代谢所决定。不饱和脂肪酸的可用性降低以及色氨酸代谢紊乱是 EAE 发展的高风险因素，而与年龄无关。酪氨酸代谢和鞘脂代谢物的变化在 15M-E 组更为显著。从这些发现可以得出结论，不饱和脂肪酸和色氨酸代谢的变化促进了 EAE 的发展，而与年龄相关的鞘脂和酪氨酸代谢的变化则是影响 EAE 发生率和严重程度的其他危险因素。
