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
DOI
10.1016/j.jneuroim.2018.06.009