Role of Jo-1 in the Immunopathogenesis of the Anti-synthetase Syndrome

Curr Rheumatol Rep. 2015 Sep;17(9):56. doi: 10.1007/s11926-015-0532-1.


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.

Publication types

  • Review

MeSH terms

  • Adaptive Immunity
  • Antibodies, Antinuclear / blood
  • Autoimmune Diseases / immunology*
  • Histidine-tRNA Ligase / immunology*
  • Humans
  • Immunity, Innate
  • Lung Diseases, Interstitial / epidemiology
  • Lung Diseases, Interstitial / immunology*
  • Myositis / epidemiology
  • Myositis / immunology*
  • Syndrome


  • Antibodies, Antinuclear
  • Jo-1 antibody
  • Histidine-tRNA Ligase