title: Type I IFN protects against murine lupus.
abstract: Both the type I (IFN-alpha beta) and type II (IFN-gamma) IFNs have been heavily implicated in the pathogenesis of systemic lupus erythematosus. To test the relative roles of these systems, congenic lupus-prone MRL/CD95(lpr/lpr) (MRL/lpr) mice lacking the type I IFN receptor (IFN-RI), type II IFN receptor (IFN-RII), or both, were derived. As expected, deficiency for IFN-RII protected MRL/lpr mice from the development of significant autoimmune-associated lymphadenopathy, autoantibodies, and renal disease. However, deficiency for the IFN-RI surprisingly worsened lymphoproliferation, autoantibody production, and end organ disease; animals doubly deficient for IFN-RI and IFN-RII developed an autoimmune phenotype intermediate between wild-type and IFN-RII-deficient animals, all correlating with an ability of type I IFN to suppress MRL B cell activation. Thus, type I IFNs protect against both the humoral and end organ autoimmune syndrome of MRL/lpr mice, independent of IFN-gamma. These findings warrant caution in the use of type I IFN antagonists in the treatment of autoimmune diseases and suggest further investigation into the interplay between the types I and II IFNs during the ontogeny of pathogenic autoantibodies.
authors.affiliation: Department of Internal Medicine , Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Hron
authors.forename: Stanford L
authors.initials: SL
authors.lastname: Peng
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D001327:Autoimmune Diseases / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D001402:B-Lymphocytes / Q000276:immunology; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D005260:Female; D016898:Interferon-alpha / Q000502:physiology*; D016899:Interferon-beta / Q000502:physiology*; D007678:Kidney Glomerulus / Q000473:pathology; D008099:Liver / Q000473:pathology; D008168:Lung / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D008181:Lupus Nephritis / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D008213:Lymphocyte Activation; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000503:physiopathology; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D019463:Mice, Inbred MRL lpr; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012217:Rheumatoid Factor / Q000096:biosynthesis; D012469:Salivary Glands / Q000473:pathology
chemical_list: D000974:Antibodies, Antinuclear; D016898:Interferon-alpha; D008565:Membrane Proteins; D017471:Receptors, Interferon; C120411:interferon receptor, type II; D053633:Receptor, Interferon alpha-beta; D016899:Interferon-beta; D012217:Rheumatoid Factor