Region-specific regulation of inflammation and pathogenesis in experimental autoimmune encephalomyelitis.
Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis and is characterized by an infiltrate of predominantly T cells and macrophages in the spinal cord and brain. In both the spinal cord and the cerebellum, Th1 cells direct inflammation to antigen-rich white matter tracts, and there is a TNFR1-dependent recruitment of CD11b(hi) cells in both regions. In the spinal cord, parenchymal invasion, demyelination and clinical symptoms are associated with TNFR1-dependant parenchymal induction (especially astrocytes) of VCAM-1 and CXCL2. None of these events occur in the cerebellum despite the fact that an inflammatory infiltrate accumulates in the perivascular space. Therefore regional specificity in astrocyte responses to inflammatory cytokines may regulate regional parenchymal infiltration and pathogenesis.
Archambault
Angela S
AS
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, USA.
Sim
Julia
J
McCandless
Erin E
EE
Klein
Robyn S
RS
Russell
John H
JH
D019264:Adoptive Transfer; D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology; D002531:Cerebellum / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D054426:Chemokine CXCL2; D018925:Chemokines / Q000378:metabolism; D004396:Coloring Agents; D003711:Demyelinating Diseases / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology*; D042783:Endothelial Cells / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology / Q000473:pathology; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein; D009413:Nerve Fibers, Myelinated / Q000276:immunology / Q000473:pathology; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D013116:Spinal Cord / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018800:Thy-1 Antigens / Q000235:genetics; D014048:Tolonium Chloride; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D039481:CD11b Antigen; D054426:Chemokine CXCL2; D018925:Chemokines; D004396:Coloring Agents; C404915:Cxcl2 protein, mouse; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D047888:Receptors, Tumor Necrosis Factor, Type I; D018800:Thy-1 Antigens; C506236:Tnfrsf1a protein, mouse; D019010:Vascular Cell Adhesion Molecule-1; D014048:Tolonium Chloride