After encounter with 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 in CNS- infiltrating cells leading to subsequent CNS pathology 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 central nervous system (CNS), resulting in disability. To assess genes which 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 naïve 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 employing CD38 knock-out (B6.129P2-Cd38tm1Lnd/J) mice, S1P-receptor modulation during EAE and quantitative expression analysis in patients with MS. The hereby defined underlying pathways indicate cellular activation and migration pathways mediated by G-protein coupled receptors as critical events in CNS tissue damage. These pathways can be further explored for novel therapeutic interventions.
- Received March 29, 2016.
- Accepted August 9, 2016.
- © 2016. Published by The Company of Biologists Ltd
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