TLR4 and autoimmune disease: Circulating estrogen levels are most closely correlated with infection resistance, and estrogen has been shown to regulate the expression of a broad array of sexually dimorphic autosomal genes in human peripheral blood cells.16 Female-biased gene ontology categories were highly enriched for various immune system functions, including TLR3 and TLR4 pathways (poly I:C and LPS responses), genes linked to the autoimmune diseases, as well as genes regulated by estrogen and LPS.