title: Suppression of experimental autoimmune encephalomyelitis by selective blockade of encephalitogenic T-cell infiltration of the central nervous system.
abstract: Multiple sclerosis (MS) is a devastating neuroinflammatory disorder of the central nervous system (CNS) in which T cells that are reactive with major components of myelin sheaths have a central role. The receptor for advanced glycation end products (RAGE) is present on T cells, mononuclear phagocytes and endothelium. Its pro-inflammatory ligands, S100-calgranulins, are upregulated in MS and in the related rodent model, experimental autoimmune encephalomyelitis (EAE). Blockade of RAGE suppressed EAE when disease was induced by myelin basic protein (MBP) peptide or encephalitogenic T cells, or when EAE occurred spontaneously in T-cell receptor (TCR)-transgenic mice devoid of endogenous TCR-alpha and TCR-beta chains. Inhibition of RAGE markedly decreased infiltration of the CNS by immune and inflammatory cells. Transgenic mice with targeted overexpression of dominant-negative RAGE in CD4+ T cells were resistant to MBP-induced EAE. These data reinforce the importance of RAGE-ligand interactions in modulating properties of CD4+ T cells that infiltrate the CNS.
authors.affiliation: Department of Pathology, College of Physicians and Surgeons of Columbia University, New York, New York, USA. sdy1@columbia.edu
authors.forename: Shirley ShiDu
authors.initials: SS
authors.lastname: Yan
authors.forename: Zhi-Ying
authors.initials: ZY
authors.lastname: Wu
authors.forename: Hui Ping
authors.initials: HP
authors.lastname: Zhang
authors.forename: Glaucia
authors.initials: G
authors.lastname: Furtado
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Shi Fang
authors.initials: SF
authors.lastname: Yan
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Schmidt
authors.forename: Chris
authors.initials: C
authors.lastname: Brown
authors.forename: Alan
authors.initials: A
authors.lastname: Stern
authors.forename: Juan
authors.initials: J
authors.lastname: LaFaille
authors.forename: Leonard
authors.initials: L
authors.lastname: Chess
authors.forename: David M
authors.initials: DM
authors.lastname: Stern
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
mesh_terms: D000818:Animals; D002460:Cell Line; D002490:Central Nervous System / Q000276:immunology / Q000502:physiology*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D039841:Leukocyte L1 Antigen Complex / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009103:Multiple Sclerosis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004676:Myelin Basic Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009418:S100 Proteins / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*
chemical_list: D039841:Leukocyte L1 Antigen Complex; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D009418:S100 Proteins; C074815:myelin basic protein 1-9