Immune System Genes Activated By Estrogen May Hold Clues To Lupus Origin
Immune system genes activated by estrogen may hold clues to lupus origin.It’s a phenomenon scientists observe whether they look at mortality rates in the United States, where medical care is relatively good, or third world nations, where medical care is often scarce: women are less likely to die from infectious diseases than men.The lower death rate has been attributed to a beneficial, yet unexplained effect estrogen has on the immune system. However, some scientists also believe that estrogen may contribute to the development of autoimmune diseases, which overwhelmingly impact pre-menopausal women, causing debilitating and deadly symptoms.
Jarjour and his team studied a family of immune response genes called toll-like receptors (TLRs), which are responsible for sending out chemical “danger signals” when a bacteria or virus is detected. These signals prompt a cascade of defenses designed to kill the pathogen; however, in a person with autoimmune disease, these inflammatory responses inexplicably turn against normal tissue. The team hypothesized that estrogen may stimulate TLR signaling, leading to a hyper-reactive immune state.“When estrogen triggers these genes to become more active, the genes tell the immune system to get ready to fight,” said Jarjour.To test their theory, scientists triggered an immune response in cells from men and women with and without lupus – an autoimmune disease that women are nine times more likely to get than men. Then, they added estrogen to see if gene activity changed, honing in on TLR8, an X chromosome-linked gene whose expression has already been implicated in the development of lupus.The addition of estrogen boosted the level of immune response in all of the study samples, but the reactivity of cells from women was almost two times greater than that of cells from men.
Margaret Shupnik, PhD, a Professor of Medicine at UVA’s School of Medicine who also worked with Jarjour’s team says she hopes that the findings will prompt other researchers to develop novel therapies that regulate TLRs, and offer lupus patients the kind of treatment options that they currently don’t have.“There has been only one new lupus treatment introduced in the past 50 years, and our most powerful drugs shut down the immune system, causing difficult-to-manage side effects,” noted Shupknik. “With evidence that TLR8 changes the way lupus patients respond to inflammation, therapies that regulate this protein might help prevent or treat this disease in ways that don’t compromise the immune system.”