HLA-DRaα1-mMOG-35-55 treatment of experimental autoimmune encephalomyelitis reduces CNS inflammation, enhances M2 macrophage frequency, and promotes neuroprotection

Gil Benedek, Roberto Meza-Romero, Kelley Jordan, Lucy Keenlyside, Halina Offner, Arthur A. Vandenbark

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Background: DRaα1-mouse(m)MOG-35-55, a novel construct developed in our laboratory as a simpler and potentially less immunogenic alternative to two-domain class II constructs, was shown previously to target the MIF/CD74 pathway and to reverse clinical and histological signs of experimental autoimmune encephalomyelitis (EAE) in DR*1501-Tg mice in a manner similar to the parent DR2β1-containing construct. Methods: In order to determine whether DRaα1-mMOG-35-55 could treat EAE in major histocompatibility complex (MHC)-mismatched mice and to evaluate the treatment effect on central nervous system (CNS) inflammation, C57BL/6 mice were treated with DRaα1-mMOG-35-55. In addition, gene expression profile was analyzed in spinal cords of EAE DR*1501-Tg mice that were treated with DRaα1-mMOG-35-55. Results: We here demonstrate that DRaα1-mMOG-35-55 could effectively treat EAE in MHC-mismatched C57BL/6 mice by reducing CNS inflammation, potentially mediated in part through an increased frequency of M2 monocytes in the spinal cord. Microarray analysis of spinal cord tissue from DRaα1-mMOG-35-55-treated vs. vehicle control mice with EAE revealed decreased expression of a large number of pro-inflammatory genes including CD74, NLRP3, and IL-1β and increased expression of genes involved in myelin repair (MBP) and neuroregeneration (HUWE1). Conclusion: These findings indicate that the DRaα1-mMOG-35-55 construct retains therapeutic, anti-inflammatory, and neuroprotective activities during treatment of EAE across MHC disparate barriers.

Original languageEnglish (US)
Article number123
JournalJournal of Neuroinflammation
Volume12
Issue number1
DOIs
StatePublished - Jun 24 2015

Keywords

  • DRaα1-mMOG-35-55 therapy
  • Experimental autoimmune encephalomyelitis (EAE)
  • M2 macrophages
  • Multiple sclerosis (MS)
  • Neuroprotection

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology
  • Neurology
  • Cellular and Molecular Neuroscience

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