Scientists at the University of British Columbia (UBC) first described the role of the thymus organ, a small gland in the immune system that is often forgotten in healthy pregnancies and is located behind the breastbone (sternum).
The study published in the journal natureemphasizes the organ’s importance in regulating immunity and metabolic control, which in turn helps prevent miscarriages and diabetes in pregnant people.
It has long been a question of how the immune system adapts to the mother and fetus during pregnancy. So researchers at UBC decided to address this problem by assessing what role the thymus might play in this process in mouse animal models.
In examining the question, the researchers found that female sex hormones that circulate during pregnancy have an important effect on the thymus and instructed the organ to produce specialized cells called regulatory T cells, also known as Tregs . These cells help regulate some of the physiological changes that take place during pregnancy that are necessary for a healthy pregnancy.
Additionally, the researchers found that specialized receptors commonly expressed in cells of the thymus, called RANK receptors, play an important role in regulating the production of these specialized Treg cells.
“We knew that RANK was expressed in the thymus, but its role in pregnancy was unknown,” said lead study author Professor Josef Penninger in a press release.
Using genetic modification, the researchers removed RANK receptors from the animals’ thymus during their investigation. “The lack of RANK prevented the production of Tregs in the thymus during pregnancy. This resulted in fewer Tregs in the placenta, which led to increased miscarriage rates,” said lead author Dr. Magdalena Paolino.
The Tregs also appear to be important for metabolic regulation during pregnancy. The study’s authors described how these cells migrated into adipose tissue in pregnant mice to prevent inflammation and regulate glucose and insulin levels. Animals lacking the RANK receptor had elevated blood glucose and insulin, including other indicators of gestational diabetes. The researchers also found that the puppies born from these animals had, on average, greater body weights than those born from normal pregnancies.
To confirm that Tregs were the major actor in these observable changes, the researchers gave animals that had been deprived of thymic RANK receptors Tregs isolated from other normal pregnancies. All changes observed were completely reversible by supplying Tregs to animals that could not produce these cells during pregnancy due to the lack of RANK receptors in the thymus.
“The discovery of this new mechanism that underlies gestational diabetes may offer new therapeutic targets for the mother and fetus in the future,” said co-author Dr. Alexandra Kautzky-Willer.
“The thymus changes massively during pregnancy and how rewiring of entire tissue like this contributes to a healthy pregnancy has been one of the remaining puzzles in immunology,” added Dr. Penninger added. “Our longstanding work has not only solved this puzzle – pregnancy hormones rewire the thymus via RANK – but also uncovered a new paradigm for its function: The thymus not only changes the mother’s immune system so that it does not reject the fetus. The thymus but also controls the mother’s metabolic health. “
“This research is changing our view of the thymus as the active and dynamic organ needed to help secure pregnancies,” concluded Penninger.