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

Zhilong Jiang, Hongmei Li, Denise C. Fitzgerald, Guang Xian Zhang*, Abdolmohamad Rostami

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

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 languageEnglish
Pages (from-to)789-799
Number of pages11
JournalEuropean Journal of Immunology
Volume39
Issue number3
DOIs
Publication statusPublished - 26 Jun 2009
Externally publishedYes

Keywords

  • Cytokine
  • EAE/MS
  • Intracellular signaling
  • MOG i.v.

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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