title: TLR7 signaling exacerbates CNS autoimmunity through downregulation of Foxp3+ Treg cells.
abstract: The innate Toll-like receptor 7 (TLR7) detects infections by recognizing viral and bacterial single-stranded RNA. In addition to pathogen-derived RNA, immune cells expressing high levels of TLR7, such as B cells and dendritic cells (DCs), can be activated by self-RNA. During myelin-induced experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, TLR7 expression is increased within the central nervous system (CNS). To define the contribution of TLR7 to the development of EAE, we evaluated the course of the disease in C57BL/6-Tlr7-deficient mice compared with that in WT mice and found that TLR7-deficient mice had decreased disease severity. This protection was associated with decreased myelin oligodendrocyte glycoprotein-specific T-cell activation by primed DCs, decreased circulating autoantibodies, attenuated inflammation within the CNS, and increased Foxp3(+) regulatory T cells in the periphery and in the CNS. In conclusion, we show that TLR7 is involved in the maintenance of autoimmunity in the pathogenesis of EAE.
authors.affiliation: Faculty of Medicine, Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland; Division of Neurology, Department of Clinical Neurosciences, Neuroimmunology Laboratory, Geneva University Hospital, Geneva, Switzerland; Division of Laboratory Medicine, Department of Genetic and Laboratory Medicine, Geneva University Hospital, Geneva, Switzerland.
authors.forename: Patrice H
authors.initials: PH
authors.lastname: Lalive
authors.forename: Mahdia
authors.initials: M
authors.lastname: Benkhoucha
authors.forename: Ngoc Lan
authors.initials: NL
authors.lastname: Tran
authors.forename: Mario
authors.initials: M
authors.lastname: Kreutzfeldt
authors.forename: Doron
authors.initials: D
authors.lastname: Merkler
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Santiago-Raber
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000235:genetics; D002490:Central Nervous System / Q000276:immunology; D004195:Disease Models, Animal; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D008213:Lymphocyte Activation / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009103:Multiple Sclerosis / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D051199:Toll-Like Receptor 7 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D008562:Membrane Glycoproteins; D063308:Myelin-Oligodendrocyte Glycoprotein; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7
keywords: EAE; IL-10; Multiple sclerosis; TLR7; Treg cell