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: Jonathan D Hron, Stanford L Peng
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 173 Issue 3 Pg. 2134-42 (Aug 01 2004) ISSN: 0022-1767 [Print] United States
• PMID: 15265950 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies, Antinuclear
• Interferon-alpha
• Membrane Proteins
• Receptors, Interferon
• interferon receptor, type II
• Receptor, Interferon alpha-beta
• Interferon-beta
• Rheumatoid Factor

Topics

• Animals
• Antibodies, Antinuclear (biosynthesis)
• Autoimmune Diseases (genetics, pathology, physiopathology, prevention & control)
• B-Lymphocytes (immunology)
• Crosses, Genetic
• Disease Models, Animal
• Female
• Interferon-alpha (physiology)
• Interferon-beta (physiology)
• Kidney Glomerulus (pathology)
• Liver (pathology)
• Lung (pathology)
• Lupus Erythematosus, Systemic (genetics, pathology, physiopathology, prevention & control)
• Lupus Nephritis (pathology, physiopathology, prevention & control)
• Lymphocyte Activation
• Lymphoproliferative Disorders (genetics, physiopathology)
• Male
• Membrane Proteins
• Mice
• Mice, Inbred BALB C
• Mice, Inbred MRL lpr
• Receptor, Interferon alpha-beta
• Receptors, Interferon (deficiency, genetics, physiology)
• Rheumatoid Factor (biosynthesis)
• Salivary Glands (pathology)