Type I Interferon controls the onset and severity of autoimmune manifestations in lpr mice

D Braun, P Geraldes, J Demengeot - Journal of autoimmunity, 2003 - Elsevier
D Braun, P Geraldes, J Demengeot
Journal of autoimmunity, 2003Elsevier
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 …
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-α 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.
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