The sex-bias in major autoimmune diseases is well known but the mechanisms are not well understood. We recently reported that chronic IFN gamma (IFNg) expression via deletion of the IFNg 3’ UTR AU-rich element (ARE-Del) mimics human primary biliary cholangitis (PBC) with a female predominance. There are female-biased immune functions including an elevated CD4/CD8 T cell ratio in the liver and spleen compared to male mice, and transfer of CD4+ T cells from ARE-Del-/- mice to female wild type mice induced moderate portal inflammation. Furthermore autoantigens, identified using peptide arrays, indicates that female ARE-Del-/- mice have a high induction of IgM reactive autoantigens associated with autoimmune diseases as compared to male mice, while the levels of IgG reactive autoantigens were not significantly different in males vs. females. Our previous gene expression data showed that interferon signaling was significantly upregulated in female ARE-Del-/- mice, so in order to determine the contribution of Type 1 interferon, we generated ARE-Del-/-/IFNaR1-/- mice which remarkably suppressed the female-biased induction of total bile acids and portal duct inflammation. Interestingly, T follicular helper cells (Tfh) and germinal center (GC) formation were increased in female ARE-Del-/- mice compared to male mice, but this difference was subsequently suppressed by deletion of IFNaR1. Therefore, the interplay of type I and type II interferons is critical for the sex-biased autoimmunity, possibly through enhanced GC formation in murine autoimmune cholangitis.