Although unclear how estrogen promotes lupus in relevant EAE, it is conceivable that estrogen may have complex multicellular effects that include altered ER signaling, stimulating pro-inflammatory cytokines from Th and other cells, augmenting pathogenic autoantibodies by favoring localized action of Th2 cells, aberrant TLR-mediated signaling, enhancing autoantigen presentation, downregulating regulatory apparatus, and dysregulating microRNA expression. The gene discussed is ESR1; the disease is systemic lupus erythematosus.