title: Human endogenous retrovirus protein activates innate immunity and promotes experimental allergic encephalomyelitis in mice.
abstract: Multiple sclerosis (MS) is a complex multifactorial disease of the central nervous system (CNS) for which animal models have mainly addressed downstream immunopathology but not potential inducers of autoimmunity. In the absence of a pathogen known to cause neuroinflammation in MS, Mycobacterial lysate is commonly used in the form of complete Freund's adjuvant to induce autoimmunity to myelin proteins in Experimental Allergic Encephalomyelitis (EAE), an animal model for MS. The present study demonstrates that a protein from the human endogenous retrovirus HERV-W family (MSRV-Env) can be used instead of mycobacterial lysate to induce autoimmunity and EAE in mice injected with MOG, with typical anti-myelin response and CNS lesions normally seen in this model. MSRV-Env was shown to induce proinflammatory response in human macrophage cells through TLR4 activation pathway. The present results demonstrate a similar activation of murine dendritic cells and show the ability of MSRV-Env to trigger EAE in mice. In previous studies, MSRV-Env protein was reproducibly detected in MS brain lesions within microglia and perivascular macrophages. The present results are therefore likely to provide a model for MS, in which the upstream adjuvant triggering neuroinflammation is the one detected in MS active lesions. This model now allows pre-clinical studies with therapeutic agents targeting this endogenous retroviral protein in MS.
authors: Geneuro, Plan-les-Ouates, Geneva, Switzerland ; Geneuro-Innovation, Lyon, France ; Université Lyon-1, Lyon, France.
authors: Hervé
authors: H
authors: Perron
authors: Hei-Lanne
authors: HL
authors: Dougier-Reynaud
authors: Christina
authors: C
authors: Lomparski
authors: Iuliana
authors: I
authors: Popa
authors: Reza
authors: R
authors: Firouzi
authors: Jean-Baptiste
authors: JB
authors: Bertrand
authors: Suzana
authors: S
authors: Marusic
authors: Jacques
authors: J
authors: Portoukalian
authors: Evelyne
authors: E
authors: Jouvin-Marche
authors: Christian L
authors: CL
authors: Villiers
authors: Jean-Louis
authors: JL
authors: Touraine
authors: Patrice N
authors: PN
authors: Marche
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D002478:Cells, Cultured; D002490:Central Nervous System; D003713:Dendritic Cells; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D015870:Gene Expression; D015686:Gene Products, env / Q000008:administration & dosage* / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000008:administration & dosage; D010446:Peptide Fragments / Q000008:administration & dosage; D011257:Pregnancy Proteins / Q000008:administration & dosage* / Q000276:immunology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000172:deficiency / Q000235:genetics / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D015686:Gene Products, env; D018950:Lipopolysaccharide Receptors; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D011257:Pregnancy Proteins; D011994:Recombinant Proteins; C495345:TLR4 protein, human; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; C445081:myelin oligodendrocyte glycoprotein (35-55); C405335:syncytin