In the present study, we tested the concept that increased amount of 17β-estradiol predisposes women to lupus by driving activation of pro-inflammatory pathways that relate to production of type 1 IFN, generation of Th17 cells by IL-21/23, generation of Th1 cells by IL-12, and regulation of IFN pathways and genes. Here, IFNA1 is linked to systemic lupus erythematosus.