Estrogen receptors in diseases of the immune system

Estrogen has distinct functions in the immune system where it acts via ERα and HERβ respectively. Surprisingly, the defects in the immune system which develop in the absence of either ERα or ERβ are quite distinct from what develops in the absence of estrogen. We have found by studying mice in which either or both estrogen receptors have been inactivated that the two estrogen receptors play distinct roles in the immune system. Loss of ERβ leads to chronic myeloid leukemia and loss of ERα leads to autoimmune disease. In mice which cannot synthesize estrogen there is also autoimmune disease resembling Sjögren's Syndrome. We plan to study these mice further with the aim of finding the exact sites of action of the two receptors in the immune system and by using specific ligands for ER α or ERβ to examine how specific parts of the immune system can be modified. These studies should lead to improved treatment of patients with diseases of the immune system.