title: Role of Jo-1 in the Immunopathogenesis of the Anti-synthetase Syndrome.
abstract: Histidyl-tRNA synthetase (HRS = Jo-1) represents a key autoantibody target in the anti-synthetase syndrome that is marked by myositis as well as extra-muscular organ complications including interstitial lung disease (ILD). Over the last 25 years, a wealth of clinical, epidemiological, genetic, and experimental data have collectively supported a role for Jo-1 in mediating deleterious cell-mediated, adaptive immune responses contributing to the disease phenotype of the anti-synthetase syndrome. Complementing these studies, more recent work suggests that unique, non-enzymatic functional properties of Jo-1 also endow this antigen with the capacity to activate components of the innate immune system, particularly cell surface as well as endosomal Toll-like receptors and their downstream signaling pathways. Combining these facets of Jo-1-mediated immunity now supports a more integrated model of disease pathogenesis that should lead to improved therapeutic targeting in the anti-synthetase syndrome and related subsets of idiopathic inflammatory myopathy.
authors.affiliation: Division of Rheumatology, Department of Medicine, Miller School of Medicine, University of Miami, RMSB, 7152, 1600 NW 10th Avenue, Miami, FL, 33136, USA, DAscherman@med.miami.edu.
authors.forename: Dana P
authors.initials: DP
authors.lastname: Ascherman
mesh_terms: D056704:Adaptive Immunity; D000974:Antibodies, Antinuclear / Q000097:blood; D001327:Autoimmune Diseases / Q000276:immunology*; D006643:Histidine-tRNA Ligase / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D017563:Lung Diseases, Interstitial / Q000453:epidemiology / Q000276:immunology*; D009220:Myositis / Q000453:epidemiology / Q000276:immunology*; D013577:Syndrome
chemical_list: D000974:Antibodies, Antinuclear; C046750:Jo-1 antibody; D006643:Histidine-tRNA Ligase