Journal
JOURNAL OF NEUROIMMUNOLOGY
Volume 322, Issue -, Pages 46-56Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jneuroim.2018.06.009
Keywords
Macrophage migration inhibitory factor; DDT; CD74; Multiple sclerosis; EAE
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Funding
- current research funds 2016 of IRCCS Centro Neurolesi Bonino Pulejo, Messina-Italy
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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.
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