title: OGR1/GPR68 Modulates the Severity of Experimental Autoimmune Encephalomyelitis and Regulates Nitric Oxide Production by Macrophages.
abstract: Ovarian cancer G protein-coupled receptor 1 (OGR1) is a proton-sensing molecule that can detect decreases in extracellular pH that occur during inflammation. Although OGR1 has been shown to have pro-inflammatory functions in various diseases, its role in autoimmunity has not been examined. We therefore sought to determine whether OGR1 has a role in the development of T cell autoimmunity by contrasting the development of experimental autoimmune encephalomyelitis between wild type and OGR1-knockout mice. OGR1-knockout mice showed a drastically attenuated clinical course of disease that was associated with a profound reduction in the expansion of myelin oligodendrocyte glycoprotein 35-55-reactive T helper 1 (Th1) and Th17 cells in the periphery and a reduced accumulation of Th1 and Th17 effectors in the central nervous system. We determined that these impaired T cell responses in OGR1-knockout mice associated with a reduced frequency and number of dendritic cells in draining lymph nodes during EAE and a higher production of nitric oxide by macrophages. Our studies suggest that OGR1 plays a key role in regulating T cell responses during autoimmunity.
authors.affiliation: Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: D'Souza
authors.affiliation: Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Fei Linda
authors.initials: FL
authors.lastname: Zhao
authors.affiliation: Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.
authors.forename: Xujian
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.|Department of Immunology, University of Toronto, Toronto, Ontario, Canada.|Women's College Research Institute, Toronto, Ontario, Canada.
authors.forename: Shannon E
authors.initials: SE
authors.lastname: Dunn
authors.affiliation: Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.|Department of Immunology, University of Toronto, Toronto, Ontario, Canada.|Department of Laboratory Medicine and Pathobiology and Immunology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000941:Antigens / Q000276:immunology; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D016207:Cytokines / Q000096:biosynthesis; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism* / Q000473:pathology*; D000939:Epitopes / Q000276:immunology; D005260:Female; D018655:Lymphocyte Count; D008264:Macrophages / Q000378:metabolism*; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000096:biosynthesis*; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology
chemical_list: D000941:Antigens; D016207:Cytokines; D000939:Epitopes; C525539:GPR68 protein, mouse; D043562:Receptors, G-Protein-Coupled; D009569:Nitric Oxide
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