title: Modulation of experimental autoimmune encephalomyelitis: effect of altered peptide ligand on chemokine and chemokine receptor expression.
abstract: Experimental autoimmune encephalomyelitis (EAE) is a T helper 1 (Th1) cell mediated demyelinating disease and the principal animal model for multiple sclerosis. Spinal cords from SJL mice primed with proteolipid protein peptide 139-151 (pPLP) expressed the chemokines RANTES, MCP-1, MIP-2, KC, MIP-1alpha, MIP-1beta, Mig, and fractalkine. We also identified IP-10 in these samples and described a sequence polymorphism in this transcript. Chemokine expression was specific for tissues of the central nervous system. MCP-1, IP-10, and MIP-2 RNA expression significantly correlated with clinical score. Chemokine receptor expression generally correlated with ligand expression. pPLP-primed mice expressed the Th1-associated markers CCR5 and CXCR3 on mononuclear cells. In addition, cells expressing CCR1, CCR2, CCR3, CCR4, CCR8, and CXCR2 were detected. Here we demonstrate that altered peptide ligand (APL)-induced protection from EAE was accompanied by modulation of chemokine and chemokine receptor expression. Spinal cord tissue sections from APL-protected mice showed greatly reduced levels of all chemokines and of CCR1, CCR5, CCR8, CXCR2 and CXCR3. The Th2-associated chemokine receptors CCR3 and CCR4 were found in protected mice, supporting the hypothesis that Th1 but not Th2 cells are down-regulated by APL treatment. This report concludes that chemokines and chemokine receptors can be useful tools to follow modulation of autoimmune disease.
authors.affiliation: Department of Pathology, Harvard Medical School, 200 Longwood Ave, Boston, MA 02115, USA.
authors.forename: F R
authors.initials: FR
authors.lastname: Fischer
authors.forename: L
authors.initials: L
authors.lastname: Santambrogio
authors.forename: Y
authors.initials: Y
authors.lastname: Luo
authors.forename: M A
authors.initials: MA
authors.lastname: Berman
authors.forename: W W
authors.initials: WW
authors.lastname: Hancock
authors.forename: M E
authors.initials: ME
authors.lastname: Dorf
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics / Q000276:immunology; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000235:genetics / Q000276:immunology; D054428:Chemokine CX3CL1; D054426:Chemokine CXCL2; D054370:Chemokine CXCL9; D018925:Chemokines / Q000235:genetics* / Q000276:immunology*; D020523:Chemokines, CX3C; D019743:Chemokines, CXC / Q000235:genetics / Q000276:immunology; D016373:DNA, Antisense; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000276:immunology; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D018991:Myelin Proteolipid Protein / Q000276:immunology / Q000494:pharmacology*; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology; D011110:Polymorphism, Genetic; D054389:Receptors, CCR1; D019713:Receptors, CCR5 / Q000235:genetics / Q000276:immunology; D054401:Receptors, CCR8; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000235:genetics* / Q000276:immunology*; D023063:Receptors, Interleukin-8B / Q000235:genetics / Q000276:immunology; D018417:Th1 Cells / Q000737:chemistry / Q000276:immunology
chemical_list: C515300:CCR1 protein, human; C103330:CCR8 protein, human; C515538:CX3CL1 protein, human; C080810:CXCL9 protein, human; C515187:CXCR3 protein, human; C515301:Ccr1 protein, mouse; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D054428:Chemokine CX3CL1; D054426:Chemokine CXCL2; D054370:Chemokine CXCL9; D018925:Chemokines; D020523:Chemokines, CX3C; D019743:Chemokines, CXC; C515539:Cx3cl1 protein, mouse; C404915:Cxcl2 protein, mouse; C515188:Cxcr3 protein, mouse; D016373:DNA, Antisense; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D019402:Macrophage Inflammatory Proteins; D008565:Membrane Proteins; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; D054389:Receptors, CCR1; D019713:Receptors, CCR5; D054401:Receptors, CCR8; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D023063:Receptors, Interleukin-8B