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Immune Disorders

18 September 2020

Gender differences in mast cells can explain why we are more susceptible to immunological diseases

Differences in biological sex can dictate our lifelong disease patterns, according to a new study.

  • Mast cells are responsible for fighting infections and helping wounds heal
  • While these cells protect against infection, they can overreact, triggering immunology diseases
  • Researchers found that mast cells often 'overreact' because of prenatal sex hormones

New research by the Michigan State University connects specific hormones present before and after birth to immune response and lifelong immunological disease development.

The study, which was published in the journal Proceedings of the National Academy of Sciences, explores why females are more at risk of some common diseases that often target the immune system – including asthma, allergies, migraines and irritable bowel syndrome.

Gender differences in our mast cells

Many immunological conditions are linked to mast cells. Mast cells are white blood cells which serve as our first line of defence against infections and any toxins present in the body. These cells also help wounds to heal.

When mast cells do their job a bit too well, they can cause chronic inflammatory diseases. And one thing that may lead to an overreactive response, is the fact that mast cells have gender differences.

According to the researchers, female mast cells store and release more inflammatory substances such as proteases, histamine and serotonin than male mast cells. Thus, female mast cells tend to have more aggressive immune responses – while this is a good thing for fighting infections, it makes females more likely to suffer from inflammatory and autoimmune diseases.

Professor Adam Moeser from the Department of Large Animal Clinical Sciences and principal study investigator explained that IBS is an example of this, as females are four times more likely to develop this condition than men.

Hormones already present at birth

Moeser stated that it’s the hormones present before birth, and not our animal sex hormones, that are more likely to influence our risk of developing mast-cell associated disorders.

"Mast cells are created from stem cells in our bone marrow," Moeser said. "High levels of perinatal androgens programme 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."

But some females exposed to male levels of perinatal androgens in the womb, are more likely to develop mast cells behaving more like those of males.

"For these females, exposure to the perinatal androgens reduced their histamine levels and they also exhibited less-severe anaphylactic responses as adults,” said Emily Macky, who’s research forms part of this study.

Improved treatment for immunological diseases

These findings could pave the way for improved treatment for sex-biased immunological and other diseases. In the future, researchers will also be able to understand better how physiological and environmental factors occurring early in life can affect our risk for disease, especially where mast cells are involved.

"While biological sex and adult sex hormones are known to have a major influence on immunological diseases between the sexes, we're learning that the hormones that we are exposed to in utero may play a larger role in determining sex differences in mast cell-associated disease risk, both as adults and as children," Moeser said.

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