Type I Interferon controls the onset and severity of autoimmune manifestations in lpr mice.
Type I Interferons (IFN-I) are immunoregulatory cytokines that enhance activation and survival of many cellular components of the immune system. In the present work, we evaluated the effect of IFN-I on the development of the lymphoproliferative disorder in Fas-defective lpr mice. We report that sustained injection of polyinosinic:polycytidylic acid, a potent inducer of IFN-I, in B6 lpr mice resulted in a dramatic aggravation of the renal disease, higher titers of autoantibodies, a 10-fold increase in serum Ig and accumulation of activated lymphocytes. Moreover, introducing a null mutation for the IFN-I-Receptor gene into the lpr background resulted in dramatic decrease of immune complexes deposition in the kidney and reduced lymphadenopathy. While several recent reports correlated serum levels of IFN-alpha with disease activity in systemic Lupus erythematosus patients, our findings establish a causal link from IFN-I production to the onset and severity of another related autoimmune syndrome.
Braun
Déborah
D
Instituto Gulbenkian de Ciência, Rua da Quinta Grande, 6, 2781-901 Oeiras, Portugal.
Geraldes
Pedro
P
Demengeot
Jocelyne
J
D000818:Animals; D001327:Autoimmune Diseases / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005921:Glomerulonephritis / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007369:Interferon Inducers / Q000494:pharmacology; D007370:Interferon Type I / Q000187:drug effects / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism; D051379:Mice; D019463:Mice, Inbred MRL lpr; D011070:Poly I-C / Q000494:pharmacology
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007369:Interferon Inducers; D007370:Interferon Type I; D011070:Poly I-C