Evidence mapPaperPMID 42018964Full record

ArticleNeurology(R) neuroimmunology & neuroinflammation2026

MIF Tautomerase Inhibition Protects Neurons From Immune-Mediated Cell Death.

Jackson W Mace, Matthew D Smith, Sachin P Gadani, Marjan Gharagozloo, Valina L Dawson, Ted M Dawson, Peter A Calabresi

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Article in Neurology(R) neuroimmunology & neuroinflammation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

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7 authors.

Jackson W MaceDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD.ORCID 0000-0001-9555-4759
Matthew D SmithDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD.ORCID 0000-0001-6614-569X
Sachin P GadaniDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD.
Marjan GharagozlooDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD.ORCID 0000-0002-2166-4012
Valina L DawsonDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD.ORCID 0000-0002-2915-3970
Ted M DawsonDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD.ORCID 0000-0002-6459-0893
Peter A CalabresiDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD.ORCID 0000-0002-7776-6472

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectivesMultiple sclerosis (MS) is characterized by peripheral immune cell infiltration into the central nervous system (CNS) and associated reactive gliosis, demyelination, and neuroaxonal degeneration. Existing therapies broadly target adaptive immune cells and treat acute inflammation but are not effective in halting chronic neurodegeneration that occurs in progressive MS. High-efficacy precision therapies that target pathways in the CNS known to contribute to MS pathophysiology are lacking. Several MS studies have identified prominent dysregulation of macrophage migration inhibitory factor (MIF), a multifunctional protein with both cytokine and enzyme activity, in inflammatory diseases. MIF is elevated in the CSF of people with MS and MIF gene variants have been linked with progressive MS, but its precise contributions to the pathophysiologic underpinnings of MS remain unclear. MIF has extracellular signaling capacity through CD74. MIF also has 2 discrete and endogenous enzymatic functions as a tautomerase and nuclease.

methodsWe used a MIF transgenic mouse line with a point mutation in the tautomerase domain (MIF-P2G) to dissect MIF's non-nuclease function during inflammation. We also utilized flow cytometry and immunohistochemistry to characterize the cellular and molecular mechanisms by which MIF tautomerase contributes to pathophysiology in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS.

resultsWe show that MIF tautomerase contributes to immune cell infiltration, glial cell proliferation, and neuroaxonal degeneration in EAE. MIF tautomerase-deficient EAE mice have reduced paralysis scores and less neuroaxonal pathology throughout the optic nerve and lumbar spinal cord. Furthermore, we show that MIF-P2G mutated mice have less peripheral immune cell trafficking and downstream reactive gliosis, neuroinflammation, and neurodegeneration during EAE. DISCUSSION: Together, this work elucidates the role of MIF's tautomerase domain in contributing to peripheral immune-mediated neurodegeneration in the context of neuroinflammatory diseases such as MS.

Indexed as

Cell DeathEncephalomyelitis, Autoimmune, ExperimentalIntramolecular OxidoreductasesMacrophage Migration-Inhibitory FactorsNeuronsAnimalsFemaleMiceMice, TransgenicIntramolecular OxidoreductasesMacrophage Migration-Inhibitory FactorsMif protein, mouse

Identifiers

PMID42018964
PMCPMC13105196

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.