New research on body fat reveals even more clearly how the female and male immune systems operate differently.
We know that men and women have different constitutions and physiology, and this is probably why men and women are more or less susceptible to different diseases.
Women, for example, they are more prone to autoimmune diseases like arthritis and lupus where the immune system attacks healthy cells.
Men, on the other hand, they are more prone to metabolic diseases which affect the way food is converted into energy. Anything that causes, in other words, conditions like obesity, hypertension or high blood sugar levels. This makes men more susceptible to diseases such as diabetes, heart disease and stroke.
To date, little evidence of differences
Until now, there was very little specific evidence of differences in the immune systems of men and women.
The new article in Nature offers researchers a new roadmap for looking for the precise cellular and molecular mechanisms at work in men and women.
The study also opens up the possibility of future drugs tailored for men and women to treat metabolic and immune diseases, as well as associated secondary diseases, including cancer. A step forward among many in the direction of longevity.
Body fat is an organ
Researchers involved in the study began to understand why men are more prone to obesity and metabolic diseases than women.
It was already known that when mice eat a high-fat diet, males become obese much faster than females. In an effort to find out why, the researchers scrutinized the mice's body fat.
"Body fat, or what we call fat, isn't just fat"says the senior author Axel Kallies, professor at the Peter Doherty Institute.
“It is actually a real organ that plays an important role in producing hormones and messenger molecules to regulate metabolism. So we looked at every cell type we could think of by isolating it from adipose and comparing males and females. "
What they found completely surprised them. They found that the immune systems that operate in the body fat of males and females they were distinctly different.
Male mice had many more different types of white blood cells called regulatory T cells (Treg cells). To be precise, males had three to four times the number of Treg cells than females.
These cells play a crucial role in limiting the otherwise harmful inflammation that triggers when our immune system is alerted to an infection.
They also found that the males had a special type of stromal cell, that is, the type of cells that make up the connective tissue that forms the organs.
"Not only did we discover dramatic differences in Treg cells, but we also discovered a type of stromal cell that responds directly to testosterone and is specific to males," says the lead author of the study Ajithkumar Vasanthakumar.
Because it was amazing
It was surprising because previous research on key organs involved in the immune system (the lymph nodes, spleen, and blood) had found no difference in Treg cells between males and females.
When they delved further to understand why males had so many other Treg cells in their body fat, they discovered male-specific stromal cells. It is these stromal cells that create the environments, or niches, for Treg cells to adapt to specific organs, such as body fat.
The team also found that male fat contained far more pro-inflammatory cytokines, the immune system's messenger molecules that allow different cells to communicate with each other and are important for triggering an immune response and inflammation.
The most surprising discovery
"This is probably the most surprising and clear finding that explains the differences in the male and female immune systems.", he claims Kallies.
"We now have a fairly complete molecular, cellular and hormonal picture of what's going on, and it could very well apply to different parts of the body, although the details of how it works can vary from organ to organ."
For example, in other organs the stroma can affect the female and male immune systems differently.
Drug tests on men and women
Another implication of the study brings us to the urgent need for medical research to end the propensity to study only male physiology and to end the underrepresentation of women in clinical trials.
A 2018 study reported that of the 10 prescription drugs that the U.S. Food and Drug Administration suspended due to serious side effects, eight caused greater risks to women's health.
"It is scandalous that drugs can only be tested on male animals. There are clinical trials that only include males when we know that the metabolism of men and women is different.", he claims Kallies. 'We need to take into account the differences between males and females from the start of the research.'
Source: University of Melbourne
