Female immunity reacts more strongly to threats: scientists have found the answer in genes

Scientists have discovered more than 1,000 genetic switches that work differently in the immune cells of men and women. These differences may explain why the female immune system reacts more actively to inflammation, but at the same time increases susceptibility to autoimmune diseases. All the details are in the Izvestia article.

Why does the female immune system react differently

Autoimmune diseases occur when the immune system mistakenly attacks the body's own healthy tissues. Women experience such diseases much more often than men. For example, systemic lupus erythematosus can be diagnosed in about nine women per man, but the reasons for this difference have not yet been sufficiently studied.

A new study by scientists from the Garvan Institute of Medical Research and the University of New South Wales, the results of which are published in the journal Science Daily, has shown that differences between male and female immunity exist at the genetic level. Researchers have discovered more than 1,000 genetic switches that work differently in the immune cells of men and women.

These differences were found to be associated with greater activity of pathways involved in inflammation in women. Such a more reactive immune system can provide an advantage in the fight against viral infections, as the body is better prepared for the threat. However, increased readiness can also have the downside of increasing the likelihood that the immune system will start attacking its own tissues.

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What the analysis of a million cells showed

Previously, it was more difficult for scientists to study such differences, since a traditional blood test shows the average activity of multiple cells at once. Because of this, the features of individual types of immune cells may remain unnoticeable. Technologies for analyzing individual cells have made it possible to examine these processes in much more detail.

Men had a higher proportion of monocytes, immune cells that are among the first to respond to threats. The activity of genes in their cells was also more closely related to the basic processes of cell maintenance and protein production.

In contrast, women had more B cells and regulatory T cells. In addition, their immune cells showed significantly higher genetic activity associated with inflammatory processes. According to scientists, it is precisely this profile that can simultaneously enhance protection against infections and increase predisposition to autoimmune diseases.

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The genetic switches were not where they were expected.

The researchers focused on the genetic switches that work in one sex but not the other. Such sites are called loci of quantitative expression features. Conventionally, they can be represented as volume controls that can enhance or weaken the activity of certain genes.

Scientists assumed that a significant part of the differences between the immune systems of men and women would be related to the X and Y sex chromosomes. However, the results turned out to be different: gender-related genetic switches were found on the sex chromosomes much less frequently than expected.

Most of the switches found were located on autosomes, non—sex chromosomes that both men and women have. In total, the researchers identified more than 1,000 such sites. By analyzing individual cells, they were able to detect genetic differences that previous studies on mixed blood samples might have concealed.

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New findings may change the treatment of autoimmune diseases

Some of the discovered genetic mechanisms were directly related to autoimmune diseases. Researchers have found variants that affect the female-specific activity of two genes associated with systemic lupus erythematosus. This may help explain why the disease is about nine times more common in women.

At the same time, scientists emphasize that genetics does not determine the risk of autoimmune disease by itself. Other factors, including hormones, also play an important role. However, the discovered genetic differences can create a certain biological basis that affects a person's susceptibility to diseases.

According to the researchers, understanding the differences between male and female immune mechanisms in the future may help create more accurate treatment methods that take into account not only the specific disease, but also the specifics of the patient's immune system.

The authors of the study believe that the data obtained also show the need to take gender into account when studying immunity and developing medical methods. If male and female autoimmune diseases develop differently, a universal approach to their treatment may not be effective enough. According to scientists, taking into account fundamental biological differences is necessary to realize the potential of personalized medicine.