title: Loss of Allograft Inflammatory Factor-1 Ameliorates Experimental Autoimmune Encephalomyelitis by Limiting Encephalitogenic CD4 T-Cell Expansion.
abstract: Experimental autoimmune encephalomyelitis (EAE), an animal model of human multiple sclerosis (MS), is mediated by myelin-specific autoreactive T cells that cause inflammation and demyelination in the central nervous system (CNS), with significant contributions from activated microglia and macrophages. The molecular bases for expansion and activation of these cells, plus trafficking to the CNS for peripheral cells, are not fully understood. Allograft inflammatory factor-1 (Aif-1) (also known as ionized Ca(2+) binding adapter-1 [Iba-1]) is induced in leukocytes in MS and EAE; here we provide the first assessment of Aif-1 function in this setting. After myelin oligodendrocyte glycoprotein peptide (MOG35-55) immunization, Aif-1-deficient mice were less likely than controls to develop EAE and had less CNS leukocyte infiltration and demyelination; their spinal cords contained fewer CD4 T cells and microglia and more CD8 T cells. These mice also showed significantly less splenic CD4 T-cell expansion and activation, plus decreased proinflammatory cytokine expression. These findings identify Aif-1 as a potent molecule that promotes expansion and activation of CD4 T cells, plus elaboration of a proinflammatory cytokine milieu, in MOG35-55-induced EAE and as a potential therapeutic target in MS.
authors.affiliation: Department of Medicine (Cardiovascular Division), Albert Einstein College of Medicine, Bronx, New York, United States of America.|Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors.forename: Prameladevi
authors.initials: P
authors.lastname: Chinnasamy
authors.affiliation: Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Lutz
authors.affiliation: Department of Medicine (Cardiovascular Division), Albert Einstein College of Medicine, Bronx, New York, United States of America.|Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors.forename: Dario F
authors.initials: DF
authors.lastname: Riascos-Bernal
authors.affiliation: Center for Autoimmune and Musculoskeletal Disease, The Feinstein Institute of Medical Research, Manhasset, New York, United States of America.
authors.forename: Venkatesh
authors.initials: V
authors.lastname: Jeganathan
authors.affiliation: Department of Medicine (Cardiovascular Division), Albert Einstein College of Medicine, Bronx, New York, United States of America.|Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors.forename: Isabel
authors.initials: I
authors.lastname: Casimiro
authors.affiliation: Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors.forename: Celia F
authors.initials: CF
authors.lastname: Brosnan
authors.affiliation: Department of Medicine (Cardiovascular Division), Albert Einstein College of Medicine, Bronx, New York, United States of America.|Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York, United States of America.|Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors.forename: Nicholas E S
authors.initials: NE
authors.lastname: Sibinga
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000172:deficiency*; D003711:Demyelinating Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000172:deficiency*; D012720:Severity of Illness Index; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
chemical_list: C491049:Aif1 protein, mouse; D002135:Calcium-Binding Proteins; D008840:Microfilament Proteins