Lineage-Specific Metabolic Properties and Vulnerabilities of T Cells in the Demyelinating Central Nervous System

The Journal of Immunology : Official Journal of the American Association of Immunologists
Scott M SekiAlban Gaultier

Abstract

Multiple sclerosis (MS) is a disease that is characterized by immune-mediated destruction of CNS myelin. Current MS therapies aim to block peripheral immune cells from entering the CNS. Although these treatments limit new inflammatory activity in the CNS, no treatment effectively prevents long-term disease progression and disability accumulation in MS patients. One explanation for this paradox is that current therapies are ineffective at targeting immune responses already present in the CNS. To this end, we sought to understand the metabolic properties of T cells that mediate ongoing inflammation in the demyelinating CNS. Using experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice, a well-studied model of MS, we showed that the CD4+ and CD8+ T cells that invade the EAE CNS are highly glycolytic. Elevated glycolytic rates in T cells isolated from the EAE CNS correlate with upregulated expression of glycolytic machinery and is essential for inflammatory responses to myelin. Surprisingly, we found that an inhibitor of GAPDH, 3-bromopyruvic acid (3-BrPa), blocks IFN-γ, but not IL-17A, production in immune cells isolated from the EAE CNS. Indeed, in vitro studies confirmed that the production of IFN-γ by differentiated Th1...Continue Reading

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Citations

Dec 8, 2017·Frontiers in Immunology·Scott M Seki, Alban Gaultier
May 22, 2019·The Journal of Clinical Investigation·Deepak Kumar KaushikV Wee Yong
Sep 26, 2019·Acta Neuropathologica·Anthony Fernández-CastañedaAlban Gaultier
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Oct 29, 2020·Science Signaling·Scott M SekiAlban Gaultier
Sep 4, 2020·Journal of Neurochemistry·Marah C RuntschStefano Angiari

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