Abstract
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 JAK/ 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/STAT signaling pathways and investigates novel therapeutic avenues for the treatment of EAE/MS.
Original language | English |
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Pages (from-to) | 789-799 |
Number of pages | 11 |
Journal | European Journal of Immunology |
Volume | 39 |
Issue number | 3 |
DOIs | |
Publication status | Published - 26 Jun 2009 |
Externally published | Yes |
Keywords
- Cytokine
- EAE/MS
- Intracellular signaling
- MOG i.v.
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology