Contribution of the macrophage migration inhibitory factor superfamily of cytokines in the pathogenesis of preclinical and human multiple sclerosis: In silico and in vivo evidences

Publication Date

2018

Journal Title

J Neuroimmunol

Abstract

© 2018 The Authors Macrophage migration inhibitory factor (MIF) is a cytokine with pleiotropic actions involved in the pathogenesis of autoimmune disorders, including Multiple Sclerosis (MS). We have first evaluated in silico the involvement of MIF, its homologue D-DT, and the receptors CD74, CD44, CXCR2 and CXCR4 in encephalitogenic T cells from a mouse model of MS, the Experimental Allergic Encephalomyelitis (EAE), as well as in circulating T helper cells from MS patients. We show an upregulation of the receptors involved in MIF signaling both in the animal model and in patients. Also, a significant increase in MIF receptors is found in the CNS lesions associated to MS. Finally, the specific inhibitor of MIF, ISO-1, improved both ex vivo and in vivo the features of EAE. Overall, our data indicate that there is a significant involvement of the MIF pathway in MS ethiopathogenesis and that interventions specifically blocking MIF receptors may represent useful therapeutic approaches in the clinical setting.

Volume Number

322

Pages

46 - 56

Document Type

Article

Status

Faculty

Facility

School of Medicine

Primary Department

Molecular Medicine

Additional Departments

General Internal Medicine

PMID

29935880

DOI

10.1016/j.jneuroim.2018.06.009

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