Printed Poster | Session 2

022 – Immunological Impact of Dietary Methionine Restriction in Preclinical Models of Multiple Sclerosis

Victoria Hannah Mamane (1) – Rutger Koning (2) – Jocelyn Chen (3) – Dominic Roy (3) – Helene Jamann (1) – Oumarou Ouedraogo (1) – Audrey Daigneault (1) – Russel Jones (4) – Catherine Larochelle (1)
CRCHUM, University of Montreal, Montreal, Canada (1) – Vrije Universiteit, Vrije Universiteit, Amsterdam, Netherlands (2) – McGill University, Department of Physiology, Montreal, Canada (3) – Van Andel Research Institute, Center for Cancer and Cell Biology, Grand Rapids, United States (4)

Background: Multiple Sclerosis (MS) is an inflammatory and demyelinating disease of the central nervous system (CNS). Pro-inflammatory CD4 TH1/TH17 are considered pathogenic in MS and its animal model, experimental autoimmune encephalomyelitis (EAE). The intestinal microbiote, a factor in T cell phenotype, is altered in MS and EAE. Moreover, obesity promote a shift towards an inflammatory immune cell phenotype and increases the risk ok developing MS, while diet influences its onset and evolution. Dietary methionine restriction (MR) without caloric restriction prolongs lifespan, decreases markers of inflammation in obese mice, and is protective in a model of inflammatory bowel disorder. However, little is known about how methionine availability affect the phenotype and function of T cells and impact T-cell mediated central neuroinflammation in MS and EAE. We found that MR affects differentiation of TH1/TH17 cells and onset of EAE, establishing a novel link between methionine metabolism and neuroinflammation.
Objectives: To characterize the potentiel of methionine availability on neuroinflammation in MS and two different EAE models.
Methods: Active MOG-induced EAE in C57BL/6 mice and spontaneous EAE in transgenic TCR1640/SJL mice (T cell receptor specific for MOG) are exposed to low methionine vs. control diet. Clinical evaluation, flow cytometry, and immunofluorescence studies are used to characterized immune cells distribution and activation, microglial activation, demyelination, and neuronal injury.
Results: Our preliminary results show that MR without caloric restriction, is associated with lower weight gain and significantly delayed onset of neurological deficits in MOG-induced EAE mice, and greatly influences onset of disease in both males and females in TCR1640 mice. This is associated with a significant reduction in the absolute number of infiltrating immune cells, in the CNS of MR mice, at peak of disease in MOG-induced EAE mice, and at presymptomatic stage in TCR1640 mice. Moreover, infiltrating immune cells, from MR mice in both animal models, express less markers of inflammation. Finally, small areas of demyelination and immune cell infiltrates were found in the spinal cord of presymptomatic TCR1640 mice on control diet, but none to few were found in the spinal cord of mice on the MR diet.
Conclusion: Our preliminary data suggest a beneficial impact of MR on clinical course and neuroinflammation in two animals models of MS and in both males and females.