ESR1 and systemic lupus erythematosus: In light of the above observations, our observations that: (i) activation of IFN-signaling up-regulates the expression of ERα (Figs. 1, 2 and 3); and (ii) E2 and IFN-signaling cooperate to activate transcription of certain target genes (Figs. 6 and 7) provide support for the idea that the female sex hormone estrogen and increased levels of IFN-α contribute to sex bias in SLE through the activation of a mutually positive feedback loop.