Inhibition of delta-like ligand 4 decreases Th1/Th17 response in a mouse model of multiple sclerosis

Neurosci Lett. 2013 Apr 29:541:161-6. doi: 10.1016/j.neulet.2013.02.038. Epub 2013 Mar 1.

Abstract

Notch is a family of receptors involved in the differentiation of several tissues, including the central nervous system and the immune system. One of the Notch ligands, delta-like 4 (Dll4), has been implicated in the differentiation of Th1 cells and the development of Th17 responses, which are involved in the pathogenesis of experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis. Our results show that a single administration of an anti-Dll4 antibody is not enough to avoid the development of EAE or to ameliorate the already established clinical signs, despite the treatment reduces the proliferative T cell responses and decreases Th1/Th17 immune responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology
  • Antibodies, Neutralizing / pharmacology
  • Antibodies, Neutralizing / therapeutic use
  • Cell Proliferation
  • Cytokines / biosynthesis
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Female
  • Intracellular Signaling Peptides and Proteins / antagonists & inhibitors*
  • Intracellular Signaling Peptides and Proteins / immunology
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Membrane Proteins / antagonists & inhibitors*
  • Membrane Proteins / immunology
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis / immunology*
  • Multiple Sclerosis / pathology
  • Spleen / drug effects
  • Spleen / pathology
  • Th1-Th2 Balance / drug effects*

Substances

  • Antibodies, Neutralizing
  • Cytokines
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • delta protein