Research ArticleMultiple Sclerosis

Teriflunomide treatment for multiple sclerosis modulates T cell mitochondrial respiration with affinity-dependent effects

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Science Translational Medicine  01 May 2019:
Vol. 11, Issue 490, eaao5563
DOI: 10.1126/scitranslmed.aao5563

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Teriflunomide tampers with T cells

Activated T cells need de novo pyrimidine biosynthesis, which has been exploited for autoimmune therapy. Klotz et al. studied samples from patients with multiple sclerosis treated with the dihydroorotate dehydrogenase inhibitor teriflunomide. They found that teriflunomide did not affect all T cells equally and led to repertoire and subset distribution changes. They also used a mouse model of T cells with higher and lower affinity for the same antigen to explore the drug’s effects. Collectively, their data demonstrate that high-affinity T cells preferentially use mitochondrial respiration, which is then inhibited by teriflunomide.