Employing metabolomic approaches to determine the influence of age on experimental autoimmune encephalomyelitis (EAE).

ABSTRACT

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.