Intravenous Administration of MOG35-55 Peptide Inhibits Experimental Autoimmune Encephalomyelitis by Suppressing IL-17/STAT4 Signaling Pathway (128.16)

Abstract

Abstract Intravenous (i.v.) administration of encephalitogenic peptide can effectively prevent experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. The mechanism underlying the induction of immune tolerance is not fully understood. In this study, we induced i.v. tolerance against EAE by administration of MOG35-55 peptide and determined the role of IL-17/STAT4 signaling pathways in this process. In EAE mice, IL-17 and tyrosine phosphorylated STAT1, STAT3, STAT4, ERK1/2 and NF-κBp65 were highly elevated in spleen cells and spinal cords, while they were significantly inhibited in tolerized mice. Administration of exogenous IL-17 effectively reversed MOG-induced immune tolerance, accompanied by an elevated level of phosphorylated STAT4. IL-17 activated STAT4 in a dose-dependent manner in vitro. CD11b+ cells in tolerant mice were tolerogenic, characterized by suppressed STAT4 activation; adoptive transfer of CD11b+ cells from the tolerized mice effectively delayed onset and reduced the severity of EAE. We conclude that the IL-17/STAT4 signaling pathway is closely related to EAE induction, which is negatively modulated in MOG-induced immune tolerance. These findings have important implications for the development of novel strategies to treat EAE/MS.