Administration of DNase diminishes BAFF induction and leads to abrogation of an E2-induced increase in type 1 IFNs and IFN-inducible genes in R4ATg mice. DNase treatment of R4ATg mice restores E2-induced BAFF mRNA levels (A) as well as serum BAFF levels (B) to that of levels observed in P-treated mice after 5 wk of treatment, whereas treatment with HI DNase did not affect E2-induced BAFF levels. C–F, An upregulation of type 1 IFNs (IFN-α,β), as well as the IFN-inducible genes ifi202 and mx1, was observed in E2-treated R4ATg mice. Administration of DNase, but not HI DNase, resulted in diminution of IFN-α, IFN-β, ifi202, and mx1 transcription to levels comparable to P-treated mice. RNA from splenocytes was analyzed for expression of BAFF and the IFN-inducible genes ifi202 and mx1, whereas RNA from mouse splenic DCs treated with serum from P, E2, E2 plus DNase, or E2 plus HI DNase R4A Tg mice was analyzed for IFN-α and IFN-β expression by real-time PCR. Unpaired t test was used to analyze the statistical differences in BAFF, ifi202, mx1, and IFN-α, and the exact Kruskal-Wallis test to determine the statistical significance in IFN-β between groups (*p < 0.04). Six to nine mice were studied per treatment group. For IFN-α and IFN-β assay, n = 3–4.