Thymus – The Key to a Successful Pregnancy?

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Thymus might be the key to a successful pregnancy, research shows
Credit: @IMBA/Kulcsar
  • A team of international researchers has discovered how the thymus regulates a mother’s immune system during pregnancy
  • The study further revealed thymus’s role in preventing gestational diabetes.
  • Findings of the study are published in the journal Nature.

Since long, scientists have wondered about the changes in the maternal immune system during pregnancy. During normal circumstances when the body detects a foreign object, the immune system starts to attack it till the threat is removed. However, that is not the case in pregnancy. Despite half the fetus containing potentially foreign DNA (from the father), the mother’s immune system continues to regard it as its own. Although previous research has shown the thymus to play an important role in adapting the maternal immune system, the molecular mechanism behind it is still not clear.

The thymus changes massively during pregnancy and how such rewiring of an entire tissue contributes to a healthy pregnancy has been one of the remaining mysteries of immunology.

Josef Penninger, Study’s Senior Author

A team of international researchers has now discovered how the thymus brings about this change. The team led by the University of British Columbia (UBC) discovered the role of the thymus in not only preventing miscarriages but also gestational diabetes. They published their findings in the journal Nature.

Molecular Insight into the Role of Thymus in Pregnancy

Thymus is a small organ located behind the sternum. It is responsible for the maturation of T-cells that are responsible for getting rid of foreign invaders. Post-puberty the thymus begins to shrink and becomes replaced by fatty tissue. Research has shown that during pregnancy the thymus increases production of regulatory T-cells. These prevents the immune system from attacking the body’s own tissue. Thus, resulting in a viable pregnancy.

According to the recently published study, female sex hormones instruct the thymus to produce specialized cells called Tregs. Furthermore, the study revealed that a receptor in the epithelium of the Thymus called RANK helps drive this mechanism. To study the effects of RANK further, the researchers investigated mice lacking the RANK gene. This resulted in decreased production of Tregs and increased rates of miscarriages among the female mice population.

The absence of RANK prevented the production of Tregs in the thymus during pregnancy. That resulted in fewer Tregs in the placentas, leading to elevated rates of miscarriage.

Magdalena Paolino, lead author

Protection from Gestational Diabetes

Gestational Diabetes is the most common metabolic disorder of pregnancy and affects approximately 18-39% of human pregnancies. The study showed that pregnant mice lacking RANK had high blood levels of insulin and glucose. This resulted in offspring with higher-than-average weight. Furthermore, when the mice were injected with thymus derived Tregs, all their health issues reversed. Including blood glucose levels and increased weights of the offspring.

Our work over many years has now not only solved this puzzle – pregnancy hormones rewire the thymus via RANK – but uncovered a new paradigm for its function: the thymus not only changes the immune system of the mother so it does not reject the fetus, but the thymus also controls metabolic health of the mother.

Josef Penninger, senior author

The study therefore establishes thymus as an important organ for a safe pregnancy.

Reference:

Paolino, M., Koglgruber, R., Cronin, S.J.F. et al. RANK links thymic regulatory T cells to fetal loss and gestational diabetes in pregnancy. Nature (2020). https://doi.org/10.1038/s41586-020-03071-0

Hellberg, Sandra, et al. “Maintained Thymic Output of Conventional and Regulatory T Cells during Human Pregnancy.” Journal of Allergy and Clinical Immunology, vol. 143, no. 2, 2019, doi:10.1016/j.jaci.2018.09.023.

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