Research at the Peter Doherty Institute for Infection and Immunity in Melbourne, recently published in Nature, has uncovered how physiological gender differences in the adipose tissue – commonly referred to as body fat – could explain why men and women are susceptible to different diseases.
Women are more prone to autoimmune diseases like arthritis, and lupus where the immune system attacks healthy cells, whereas men are more prone to metabolic diseases resulting in conditions like obesity, high blood pressure, diabetes and heart disease.
That gender differences in immune systems caused this propensity was already known. What this research uncovered was the specifics of how female and male immune systems operate differently. Speaking to Indian Link from Melbourne, lead author of the research Dr. Ajithkumar Vasanthakumar tried to explain the complex science and intricacies of their
research. Their research was on regulatory T-cells (Treg cells) in the adipose tissue, whose primary function is to prevent autoimmunity.
“A cardinal feature of the immune system is to distinguish between cells that belong to you and cells that come from the outside,” he explained. “The immune system reacts only when
attacked from outside and generally will not act against your own cells. Very rarely will the immune system attack your own cells – and this can cause diseases such as arthritis, pancreatitis, multiple sclerosis, etc, collectively called auto-immune diseases. Treg cells efficiently block the immune cells that act against your own body, thus preventing autoimmune diseases. Treg cells also play a crucial role in limiting inflammation in the adipose tissue. When inflammation in this tissue exceeds a threshold, it causes insulin resistance and Type-2 diabetes.”
It is already well known that when a high-fat diet is fed to mice, male mice become obese faster than the females. What Dr. Ajithkumar and his team did was to examine the body fat of mice in finer detail. They took a deep dive into the cellular underpinnings of the adipose tissue, simultaneously comparing differences in males and females. They discovered that male mice typically have three to four times more Treg cells than females.
Past research on key organs involved in the immune system, such as the lymph nodes, spleen, and blood, had found no difference in Treg cells between males and females.
Investigating body fat for its influence on the immune system was novel. “Not only did we discover dramatic differences in Treg cells, but we also discovered a stromal cell type that responds directly to testosterone, a hormone specific to males,” he revealed, adding that the estrogen hormone in females helps to counteract inflammation in the adipose tissue. The testosterone hormone in males has the opposite effect and hence males have more Treg cells to counteract this propensity to inflammation.
Elaborating on why body fat was chosen as the focal point of their research, he said, “Body fat is actually an organ that has a much greater role than just being a storehouse of energy. It also plays an important role in making hormones and regulates metabolism.”
In an earlier study, these researchers had found the same type of Treg cells in human adipose tissue as in mice, so they believe that similar systems are at play. This particular study which focussed on body fat succeeded in providing a fairly complete picture of cells in the adipose tissue and how they behaved very differently for males and females.
Dr. Ajithkumar believes that the findings will initiate more of such research. Until now preference has been given to male mice for research into metabolism as female mice take longer to respond to a high-fat diet. He reckons that scientists need to ensure an equal representation of sexes in their research, both in laboratories and clinical trials.
The implications of this important piece of research could be ground-breaking. Dr Ajithkumar postulated, “Hopefully in the near future, gender-specific drugs will be made as this proves that the physiology of men and women is markedly different at the cellular level. Clinical trials should have equal representation of males and females. It could well be males and females need different dosages of a drug.”
He added that this research could have implications in the treatment of diseases like cancers too. One of the current therapies for prostate cancer is ‘androgen deprivation therapy’ where production of testosterone is slowed. Similarly in women with ovarian or breast cancer, as one of the treatments, estrogen is suppressed. “Our research proves that modifying hormone levels affect metabolic health and this needs further investigation.”
The Doherty Institute’s primary focus is infectious diseases and the institute was the first in the world to have successfully grown the novel coronavirus from a patient sample. This will help scientists around the world to develop a potential vaccine. The panacea for coronavirus may be some time away. As an aside and parting advice, Dr. Ajith advises all to follow proper hand hygiene, adding, “Stay away from crowds if possible. Exercising and building one’s general immunity is always helpful.”
