New Important Insights into the Role of the Thymus in Successful Pregnancies

Magdalena Paolino. Photo: the Ragnar Söderberg Foundation

To prevent miscarriages and gestational diabetes, important changes occur in the thymus during pregnancies. This was shown in a study published in the journal Nature by an international group of researchers and led from Karolinska Institutet. The first and corresponding author is assistant professor and CMMer Magdalena Paolino. The publication is the result of a close collaboration between the laboratory of Magdalena Paolino at Karolinska Institutet/CMM and the laboratories of Josef Penninger at IMBA and UBC.

The thymus is an immune organ where the T cells mature in order to migrate into the blood stream and tissues and perform their specialized functions within the immune system. The regulatory T cells (or Tregs) function as regulators of other T cells.

Magdalena Paolino and her co-workers discovered that through a mechanism that involves RANK, a receptor expressed in the thymus epithelia, female sex hormones instruct the thymus to produce Tregs specialized in dealing with physiological changes during pregnancy.

Deletion of RANK in mice resulted in a prevented production of Tregs in the thymus and fewer Tregs in the placentas, leading to miscarriages.

They further found that the deletion of RANK influenced the glucose metabolism in the pregnant mice, giving rise to several indicators of gestational diabetes and overweight, diabetes-prone offspring.

The researchers subsequently showed that women with gestational diabetes had a reduced number of Tregs in their placentas.

For more information, please read the Karolinska Institutet press release and the publication:

“RANK links thymic Tregs to fetal loss and gestational diabetes in pregnancy”, Magdalena Paolino, Rubina Koglgruber, Shane J. F. Cronin, Iris Uribesalgo, Esther Rauscher, Juergen Harreiter, Michael Schuster, Dagmar Bancher-Todesca, Blanka Pranjic, Maria Novatchkova, Andrea White, Verena Sigl, Sabine Dekan, Juan P. Fededa, Thomas Penz, Christoph Bock, Lukas Kenner, Georg A. Holländer, Graham Anderson, Alexandra Kautzky-Willer, and Josef M. Penninger, Nature, online December 23, 2020, DOI: 10.1038/s41586-020-03071-0