title: HLA-DRα1-mMOG-35-55 treatment of experimental autoimmune encephalomyelitis reduces CNS inflammation, enhances M2 macrophage frequency, and promotes neuroprotection.
abstract: BACKGROUND
  DRα1-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 DRα1-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 DRα1-mMOG-35-55. In addition, gene expression profile was analyzed in spinal cords of EAE DR*1501-Tg mice that were treated with DRα1-mMOG-35-55.
  
  
  RESULTS
  We here demonstrate that DRα1-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 DRα1-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).
  
  
  CONCLUSIONS
  These findings indicate that the DRα1-mMOG-35-55 construct retains therapeutic, anti-inflammatory, and neuroprotective activities during treatment of EAE across MHC disparate barriers.
authors.affiliation: Neuroimmunology Research, VA Portland Health Care System, Portland, OR, USA.|Tykeson MS Research Laboratory, Department of Neurology UHS-46, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR, USA.
authors.forename: Gil
authors.initials: G
authors.lastname: Benedek
authors.affiliation: Neuroimmunology Research, VA Portland Health Care System, Portland, OR, USA.|Tykeson MS Research Laboratory, Department of Neurology UHS-46, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR, USA.
authors.forename: Roberto
authors.initials: R
authors.lastname: Meza-Romero
authors.affiliation: Tykeson MS Research Laboratory, Department of Neurology UHS-46, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR, USA.
authors.forename: Kelley
authors.initials: K
authors.lastname: Jordan
authors.affiliation: Tykeson MS Research Laboratory, Department of Neurology UHS-46, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR, USA.
authors.forename: Lucy
authors.initials: L
authors.lastname: Keenlyside
authors.affiliation: Neuroimmunology Research, VA Portland Health Care System, Portland, OR, USA.|Tykeson MS Research Laboratory, Department of Neurology UHS-46, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR, USA.|Department of Anesthesiology and Perioperative Medicine, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Halina
authors.initials: H
authors.lastname: Offner
authors.affiliation: Neuroimmunology Research, VA Portland Health Care System, Portland, OR, USA. vandenba@ohsu.edu.|Tykeson MS Research Laboratory, Department of Neurology UHS-46, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR, USA. vandenba@ohsu.edu.|Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, OR, USA. vandenba@ohsu.edu.
authors.forename: Arthur A
authors.initials: AA
authors.lastname: Vandenbark
mesh_terms: D000818:Animals; D018845:CD11 Antigens / Q000378:metabolism; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D002493:Central Nervous System Diseases / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000473:pathology; D059805:HLA-DR alpha-Chains / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D037181:Lectins, C-Type / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use*; D009416:Nerve Regeneration / Q000187:drug effects; D000066829:Neuroprotection / Q000187:drug effects; D018696:Neuroprotective Agents / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use; D011956:Receptors, Cell Surface / Q000378:metabolism
chemical_list: D018845:CD11 Antigens; D059805:HLA-DR alpha-Chains; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D063308:Myelin-Oligodendrocyte Glycoprotein; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; C445081:myelin oligodendrocyte glycoprotein (35-55)