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Ifn-Gamma Au-Rich Element Removal Promotes Chronic Ifn-Gamma Expression And Autoimmunity In Mice, Deborah L. Hodge, Cyril Berthet, Vincenzo Coppola, Wolfgang Kastenmüller, Matthew D. Buschman, Paul M. Schaughency, Hidekazu Shirota, Anthony J. Scarzello, Jeff J. Subleski, Miriam R. Anver, John R. Ortaldo, Fanching Lin, Della A. Reynolds, Michael E. Sanford, Philipp Kaldis, Lino Tessarollo, Dennis M. Klinman, Howard A. Young Sep 2014

Ifn-Gamma Au-Rich Element Removal Promotes Chronic Ifn-Gamma Expression And Autoimmunity In Mice, Deborah L. Hodge, Cyril Berthet, Vincenzo Coppola, Wolfgang Kastenmüller, Matthew D. Buschman, Paul M. Schaughency, Hidekazu Shirota, Anthony J. Scarzello, Jeff J. Subleski, Miriam R. Anver, John R. Ortaldo, Fanching Lin, Della A. Reynolds, Michael E. Sanford, Philipp Kaldis, Lino Tessarollo, Dennis M. Klinman, Howard A. Young

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We generated a mouse model with a 162 nt AU-rich element (ARE) region deletion in the 3' untranslated region (3'UTR) of the interferon-gamma (IFN-γ) gene that results in chronic circulating serum IFN-γ levels. Mice homozygous for the ARE deletion (ARE-Del) (-/-) present both serologic and cellular abnormalities typical of patients with systemic lupus erythematosus (SLE). ARE-Del(-/-) mice display increased numbers of pDCs in bone marrow and spleen. Addition of IFN-γ to Flt3-ligand (Flt3L) treated in vitro bone marrow cultures results in a 2-fold increase in pDCs with concurrent increases in IRF8 expression. Marginal zone B (MZB) cells and marginal zone …