IL-12Rβ2 has a protective role in relapsing-remitting experimental autoimmune encephalomyelitis

J Neuroimmunol. 2016 Feb 15:291:59-69. doi: 10.1016/j.jneuroim.2015.12.009. Epub 2015 Dec 21.

Abstract

IL-12Rβ2 is a common receptor subunit of heterodimeric receptors for IL-12 and IL-35, two cytokines that are implicated in immunopathogenesis of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. We evaluated the role of IL-12Rβ2 in relapsing-remitting EAE (RR-EAE). IL-12Rβ2-deficient SJL/J mice developed markedly more severe clinical EAE, and had greater mortality and more severe relapses compared with wild-type controls. IL-12Rβ2-deficient EAE mice also had more infiltrating mononuclear cells in the CNS, as well as higher T cell proliferative capacity and decreased IFN-γ production at the periphery. These findings demonstrate a protective role of IL-12Rβ2 in RR-EAE.

Keywords: Experimental autoimmune encephalomyelitis (EAE); IL-12; IL-12Rβ2; IL-35; Relapse.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Proliferation / drug effects
  • Central Nervous System / pathology*
  • Cytokines / metabolism
  • Disease Models, Animal
  • Encephalomyelitis, Autoimmune, Experimental / chemically induced
  • Encephalomyelitis, Autoimmune, Experimental / genetics
  • Encephalomyelitis, Autoimmune, Experimental / pathology*
  • Encephalomyelitis, Autoimmune, Experimental / prevention & control*
  • Flow Cytometry
  • Freund's Adjuvant
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myelin Proteolipid Protein / toxicity
  • Neutrophil Infiltration / genetics
  • Peptide Fragments / toxicity
  • Receptors, Interleukin-12 / deficiency*
  • Receptors, Interleukin-12 / genetics
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Time Factors

Substances

  • Cytokines
  • Myelin Proteolipid Protein
  • Peptide Fragments
  • Receptors, Interleukin-12
  • myelin proteolipid protein (139-151)
  • Freund's Adjuvant