Mutually Positive Regulatory Feedback Loop between Interferons and Estrogen Receptor-α in Mice: Implications for Sex Bias in Autoimmunity

摘要: Background Systemic lupus erythematosus (SLE), an autoimmune disease, predominantly affects women of childbearing age. Moreover, increased serum levels interferon-alpha (IFN-alpha) are associated with the disease. Although, female sex hormone estrogen (E2) is implicated in bias SLE through up-regulation IFN-gamma expression, molecular mechanisms remain unknown. Here we report that activation IFN (alpha or gamma)-signaling immune cells up-regulates expression receptor-alpha (ERalpha; encoded by Esr1 gene) and stimulates target genes. Methodology/principal findings We found treatment mouse splenic cell lines gamma) steady-state ERalpha mRNA protein. The increase was primarily due to transcriptional it dependent upon signal transducer activator transcription-1 (STAT1) factor IFN. IFN-treatment also stimulated transcription a reporter gene, which driven promoter region murine gene. Notably, from pre-autoimmune lupus-prone (NZB x NZW)F(1) mice had relatively higher mRNAs ERalpha-responsive genes as compared age-matched males. Conclusions/significance Our observations identify novel mutually positive regulatory feedback loop between IFNs support idea this contributes SLE.