New work may help explain why some autoimmune or immune-related diseases are more common in women, who are more likely to have disorders like allergies, irritable bowel syndrome, and asthma. Researchers have connected the hormones that are present before and after birth with a lifetime risk of immune disease, and immune response. The findings, which may help open up new therapeutic options, have been reported in the Proceedings of the National Academy of Sciences.
"This research shows that it's our perinatal hormones, not our adult sex hormones, that have a greater influence on our risk of developing mast cell-associated disorders throughout the lifespan," said the principal investigator of the study Adam Moeser, the Matilda R. Wilson Endowed Chair and professor in the Department of Large Animal Clinical Sciences at Michigan State University. "A better understanding of how perinatal sex hormones shape lifelong mast cell activity could lead to sex-specific preventatives and therapies for mast cell-associated diseases."
The immune system has many cell types, including mast cells, which serve multiple purposes; they can defend against invaders, help control the immune response, and play a role in wound healing. However, their activity has to be regulated. When they are overactive, they can trigger chronic inflammatory diseases and may even lead to death in some cases.
Previous work by Moeser has shown that there are sex differences in mast cells: in females, mast cells carry and release more substances that promote inflammation, like histamine, proteases, and serotonin, compared to men. This makes them more likely to initiate an aggressive immune response. So while females may have a slight advantage when it comes to fighting infections, they are also at greater risk for inflammatory and immune diseases.
"IBS is an example of this," said researcher Emily Mackey. "While approximately 25 percent of the U.S. population is affected by IBS, women are up to four times more likely to develop this disease than men."
The researchers found that there are lower levels of serum histamine and anaphylactic reactions are less severe in males because their sex-specific hormone levels are higher at birth. These hormones are called perinatal androgens.
"Mast cells are created from stem cells in our bone marrow. High levels of perinatal androgens program the mast cell stem cells to house and release lower levels of inflammatory substances, resulting in a significantly reduced severity of anaphylactic responses in male newborns and adults," Moeser said.
"We then confirmed that the androgens played a role by studying males who lack functional androgen receptors," said study author Cynthia Jordan, a professor of Neuroscience.
When females were exposed to male levels of perinatal androgens in utero, their mast cells become more like those in males.
"For these females, exposure to the perinatal androgens reduced their histamine levels and they also exhibited less-severe anaphylactic responses as adults," added Mackey.