A small gland hidden behind the sternum has proven essential for a pregnancy to come to fruition without complications. This organ also works to prevent miscarriage and diabetes in pregnant women. The organ in question is the thymus, and a study published today in the journal « Nature»Reveals its important role in both metabolic control and immunity during pregnancy.
How the immune system adapts to support mother and fetus has puzzled researchers for decades. The study, conducted by a research team, coordinated by Josef Penninger of the University of British Columbia (Canada), now provides an answer.
Researchers have found that female sex hormones promote major changes in the thymus, a central organ of the immune system, to produce specialized cells, called Tregs, whose function is to cope with the physiological changes that arise during pregnancy.
They also identified RANK, a receptor expressed in a part of the thymus – epithelium – as the key molecule behind this mechanism. “We knew that RANK was expressed in the thymus, but its role in pregnancy was unknown,” says Penninger.
The authors studied mice in which the RANK receptor had been removed from the thymus. «The absence of RANK prevented the production of Tregs in the thymus during pregnancy. This led to a lack of Tregs cells in the placentas, leading to high rates of miscarriage.», Explains the main author of the study, Magdalena Paolino, from Karolinska Institute (Sweden).
The findings also offer new molecular information on the development of gestational diabetes, a disease that affects approximately 15% of pregnant women worldwide and yet puzzles scientists.
In healthy pregnancies, the researchers found that Treg cells migrated to the mother’s fat tissue to prevent inflammation and help control glucose levels in the body. Pregnant mice lacking RANK had high blood glucose and insulin levels and many other indicators of gestational diabetes, including larger-than-average pups.
“Like the babies of women with gestational diabetes, the newborn puppies were much more obese,” says Paolino.
Tregs deficiency during pregnancy in mothers also led to long-lasting transgenerational effects in the offspring, who remained prone to diabetes and being overweight throughout their lives.
Interestingly, administering thymus-derived Treg cells isolated from normal pregnancies to RANK-deficient mice reversed all the mice’s health problems, including miscarriage and maternal glucose levels, and also normalized the body weight of the pups. .
The researchers also analyzed a group of women with gestational diabetes, revealing a reduced number of Tregs cells in their placentas, similar to the study in mice. “The discovery of this new mechanism underlying gestational diabetes offers new therapeutic targets for the mother and fetus in the future,” notes co-author Alexandra Kautzky-Willer of the Vienna Medical University (Austria).
“Our work over many years has not only solved this puzzle (pregnancy hormones reconnect the thymus through RANK) but has discovered a new paradigm for its function: the thymus not only changes the mother’s immune system so that it does not reject the fetus, but also controls the mother’s metabolic health.
“This research changes our view of the thymus as an active and dynamic organ necessary to protect pregnancies,” concludes Penninger.