Estrogen was also shown to exacerbate lupus disease severity via an ERα-independent mechanism along with other immune effects contributing to lupus pathogenesis, including modulation of Toll-like receptor (TLR) pathways, dendritic cell development, or E2-TWEAK signaling (Scott et al., 2017). This evidence concerns the gene TNFSF12 and systemic lupus erythematosus.