title: Identification of gene expression patterns crucially involved in experimental autoimmune encephalomyelitis and multiple sclerosis.
abstract: After encounter with a central nervous system (CNS)-derived autoantigen, lymphocytes leave the lymph nodes and enter the CNS. This event leads only rarely to subsequent tissue damage. Genes relevant to CNS pathology after cell infiltration are largely undefined. Myelin-oligodendrocyte-glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis (MS), a chronic autoimmune disease of the CNS that results in disability. To assess genes that are involved in encephalitogenicity and subsequent tissue damage mediated by CNS-infiltrating cells, we performed a DNA microarray analysis from cells derived from lymph nodes and eluted from CNS in LEW.1AV1 (RT1av1) rats immunized with MOG 91-108. The data was compared to immunizations with adjuvant alone or naive rats and to immunizations with the immunogenic but not encephalitogenic MOG 73-90 peptide. Here, we show involvement of Cd38, Cxcr4 and Akt and confirm these findings by the use of Cd38-knockout (B6.129P2-Cd38tm1Lnd/J) mice, S1P-receptor modulation during EAE and quantitative expression analysis in individuals with MS. The hereby-defined underlying pathways indicate cellular activation and migration pathways mediated by G-protein-coupled receptors as crucial events in CNS tissue damage. These pathways can be further explored for novel therapeutic interventions.
authors: Department of General Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, 72076 Tübingen, Germany.
authors: Martin M
authors: MM
authors: Herrmann
authors: Department of General Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, 72076 Tübingen, Germany.
authors: Silvia
authors: S
authors: Barth
authors: Department of General Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, 72076 Tübingen, Germany.
authors: Bernhard
authors: B
authors: Greve
authors: Department of General Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, 72076 Tübingen, Germany.
authors: Kathrin M
authors: KM
authors: Schumann
authors: Department of General Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, 72076 Tübingen, Germany.
authors: Andrea
authors: A
authors: Bartels
authors: Department of General Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, 72076 Tübingen, Germany Department of Neurology, University of Regensburg, 93053 Regensburg, Germany robert.weissert@ukr.de.
authors: Robert
authors: 0000-0002-1295-1271
authors: R
authors: Weissert
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics* / Q000473:pathology; D005260:Female; D000068876:Fingolimod Hydrochloride / Q000494:pharmacology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007114:Immunization; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000235:genetics* / Q000473:pathology; D063308:Myelin-Oligodendrocyte Glycoprotein; D010455:Peptides; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology
chemical_list: D054377:Chemokine CXCL12; D063308:Myelin-Oligodendrocyte Glycoprotein; D010455:Peptides; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D051997:ADP-ribosyl Cyclase 1; D000068876:Fingolimod Hydrochloride
keywords: Adjuvant; Cellular traffic; Central nervous system; Experimental autoimmune encephalomyelitis; Multiple sclerosis; T cell