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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.

Abstract：

: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.

journal_name

J Neuroimmunol

journal_title

Journal of neuroimmunology

authors

Fagone P,Mazzon E,Cavalli E,Bramanti A,Petralia MC,Mangano K,Al-Abed Y,Bramati P,Nicoletti F

doi

10.1016/j.jneuroim.2018.06.009

subject

Has Abstract

pub_date

2018-09-15 00:00:00

pages

46-56

eissn

0165-5728

issn

1872-8421

pii

S0165-5728(18)30141-3

journal_volume

322

pub_type

杂志文章

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