TY - JOUR
T1 - Contribution of the macrophage migration inhibitory factor superfamily of cytokines in the pathogenesis of preclinical and human multiple sclerosis
T2 - In silico and in vivo evidences
AU - Fagone, Paolo
AU - Mazzon, Emanuela
AU - Cavalli, Eugenio
AU - Bramanti, Alessia
AU - Petralia, Maria Cristina
AU - Mangano, Katia
AU - Al-Abed, Yousef
AU - Bramanti, Placido
AU - Nicoletti, Ferdinando
N1 - Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.
PY - 2018/9/15
Y1 - 2018/9/15
N2 - 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.
AB - 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.
U2 - 10.1016/j.jneuroim.2018.06.009
DO - 10.1016/j.jneuroim.2018.06.009
M3 - Article
C2 - 29935880
VL - 322
SP - 46
EP - 56
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
SN - 0165-5728
ER -