Leukocyte recruitment during onset of experimental allergic encephalomyelitis is CCR1 dependent

Eur J Immunol. 2000 Aug;30(8):2372-7. doi: 10.1002/1521-4141(2000)30:8<2372::AID-IMMU2372>3.0.CO;2-D.


We have shown that macrophages and microglia present within demyelinating plaques of patients with multiple sclerosis (MS) are immunoreactive for the chemokine receptor CCR1 and its ligand, macrophage inflammatory protein-1alpha. To test the importance of CCR1 to the pathogenesis of MS, we studied the progression of experimental allergic encephalomyelitis (EAE) in CCR1(+/+) vs. CCR1(-/-) mice. After immunization with myelin oligodendrocyte glycoprotein (MOG) 35-55 peptide, nearly all CCR1(+/+) mice developed EAE (95% incidence, severity 2.5+/-0.1), whereas CCR1(-/-) mice had less severe disease (55% incidence, p<0.001; severity 1. 2+/-0.2, p<0.001). CCR1(+/+) mice showed elevated brain mRNA for the chemokines immune protein (IP)-10, RANTES and monocyte chemoattractant protein-1 prior to disease onset, whereas only IP-10 mRNA was elevated in CCR1(-/-) mice. Both groups of mice had comparable in vitro lymphocyte proliferation and cytokine production upon stimulation with MOG peptide, and similar cutaneous hypersensitivity responses to 2,4-dinitrofluorobenzene, suggesting that CCR1(-/-) mice were not systemically immunosuppressed. These data demonstrate that deletion of a chemokine receptor is at least partially protective in EAE, and suggest that targeting of CCR1 may be of therapeutic significance clinically.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement
  • Chemokine CCL2 / genetics
  • Chemokine CCL4
  • Chemokine CCL5 / genetics
  • Cytokines / biosynthesis
  • Encephalomyelitis, Autoimmune, Experimental / etiology*
  • Encephalomyelitis, Autoimmune, Experimental / therapy
  • Immunization
  • Leukocytes / physiology*
  • Macrophage Inflammatory Proteins / genetics
  • Mice
  • RNA, Messenger / analysis
  • Receptors, CCR1
  • Receptors, Chemokine / physiology*
  • Skin / immunology


  • Ccr1 protein, mouse
  • Chemokine CCL2
  • Chemokine CCL4
  • Chemokine CCL5
  • Cytokines
  • Macrophage Inflammatory Proteins
  • RNA, Messenger
  • Receptors, CCR1
  • Receptors, Chemokine