MOG35–55 i.v suppresses experimental autoimmune encephalomyelitis partially through modulation of Th17 and JAK/STAT pathways

SUMMARY Intravenous (i.v.) administration of encephalitogenic peptide can effectively prevent experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis; however, the underlying cellular and molecular mechanisms are not fully understood. In this study, we induced i.v. tolerance to EAE by administration of MOG35-55 peptide and determined the effect of this approach on intracellular signaling pathways of the IL-23/IL-17 system, which is essential for the pathogenesis of MS/EAE. In tolerized mice, phosphorylation of Janus kinase (Jak)/signal transducer and activator of transcription (STAT)-1, -4, ERK1/2 and NF-κBp65 were significantly reduced in splenocytes and the central nervous system. MOG i.v. treatment led to significantly lower production of IL-17, and administration of exogenous IL-17 slightly broke immune tolerance, which was associated with reduced activation of STAT4 and NF-κB. Suppressed phosphorylation of these pathway molecules was primarily evident in CD11b + and small numbers of CD4 + , CD8 + and CD11c + cells. More importantly, adoptive transfer of CD11b + splenocytes of tolerized mice effectively delayed onset and reduced clinical severity of actively induced EAE. This study correlates MOG i.v. tolerance with modulation of Jak/STATs signaling pathways and investigates novel therapeutic avenues for the treatment of EAE/MS.