CCR4 contributes to the pathogenesis of experimental autoimmune encephalomyelitis by regulating inflammatory macrophage function

J Neuroimmunol. 2011 Jul;236(1-2):17-26. doi: 10.1016/j.jneuroim.2011.04.008. Epub 2011 May 14.

Abstract

Chemokines and their receptors play a critical role in orchestrating the immune response during experimental autoimmune encephalomyelitis (EAE). Expression of CCR4 and its ligand CCL22 has been observed in ongoing disease. Here we describe a role for CCR4 in EAE, illustrating delayed and decreased disease incidence in CCR4(-/-) mice corresponding with diminished CNS infiltrate. Peripheral T cell responses were unaltered in CCR4(-/-) mice; rather, disease reduction was related to reduced CD11b(+)Ly6C(hi) inflammatory macrophage (iMϕ) numbers and function. These results provide evidence that CCR4 regulates EAE development and further supports the involvement of CCR4 in iMϕ effector function.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Encephalomyelitis, Autoimmune, Experimental / etiology
  • Encephalomyelitis, Autoimmune, Experimental / metabolism*
  • Encephalomyelitis, Autoimmune, Experimental / pathology*
  • Female
  • Inflammation Mediators / physiology*
  • Macrophages / metabolism
  • Macrophages / pathology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Molecular Sequence Data
  • Receptors, CCR4 / physiology*

Substances

  • Ccr4 protein, mouse
  • Inflammation Mediators
  • Receptors, CCR4