title: Absence of reuptake of serotonin influences susceptibility to clinical autoimmune disease and neuroantigen-specific interferon-gamma production in mouse EAE.
abstract: Serotonin (5-hydroxytryptamine, 5-HT) is one of the most extensively studied neurotransmitters of the central nervous system. It also has been identified in constituents of the immune system. Therefore serotonin has been suggested to serve as a mediator of bidirectional interactions between the nervous system and the immune system. We investigated this interaction in experimental autoimmune encephalomyelitis (EAE), a well-defined animal model of autoimmune disease of the central nervous system (CNS) mimicking features of the human disease multiple sclerosis. EAE was induced by immunization with the autoantigens myelin basic protein (MBP) or the immunodominant peptide of myelin oligodendrocyte glycoprotein (MOG) spanning amino acids 35-55 (MOGp 35-55). We studied EAE in knockout (KO) mice lacking the 5-HT transporter (5-HTT) on a C57.BL/6 background, in comparison with wild-type C57.BL/6 animals. After immunization with MOGp 35-55, or with rat MBP, the disease courses of the 5-HTT knockout mice were attenuated as compared to wildtype control mice. This difference was more pronounced in female animals. To dissect potential immune mechanisms underlying this phenomenon, histological studies of the CNS and cytokine measurements in mononuclear cells from the spleens of 5-HTT KO mice and wild-type controls were performed. We found a reduction of the inflammatory infiltrate in the CNS and of the neuroantigen-specific production of IFN-gamma in splenocytes, again accompanied by a gender difference. These findings suggest a potential role of extracellular 5-HT homeostasis in the fine-tuning of neuroantigen-specific immune responses.
authors.affiliation: Clinical Research Group for Multiple Sclerosis, Department of Neurology, University of Würzburg, Germany.
authors.forename: H H
authors.initials: HH
authors.lastname: Hofstetter
authors.forename: R
authors.initials: R
authors.lastname: Mössner
authors.forename: K P
authors.initials: KP
authors.lastname: Lesch
authors.forename: R A
authors.initials: RA
authors.lastname: Linker
authors.forename: K V
authors.initials: KV
authors.lastname: Toyka
authors.forename: R
authors.initials: R
authors.lastname: Gold
mesh_terms: D000208:Acute Disease; D000818:Animals; D001324:Autoantigens / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002490:Central Nervous System / Q000276:immunology; D004198:Disease Susceptibility / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism; D000939:Epitopes / Q000276:immunology; D005260:Female; D006023:Glycoproteins / Q000276:immunology; D007150:Immunohistochemistry / Q000379:methods; D007371:Interferon-gamma / Q000276:immunology*; D007378:Interleukins / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D004676:Myelin Basic Protein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000276:immunology; D051381:Rats; D012701:Serotonin / Q000276:immunology* / Q000493:pharmacokinetics; D012737:Sex Factors; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D001324:Autoantigens; D000939:Epitopes; D006023:Glycoproteins; D007378:Interleukins; D004676:Myelin Basic Protein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55); D012701:Serotonin; D007371:Interferon-gamma