19 February 2015

The immune system of the mother-to-be is a deadly threat to the foetus, and must therefore be weakened during pregnancy. New research shows that this adjustment is controlled by the placenta.

The foetus gets half of its genetic material from the father, which means it is perceived as an intruder in the mother’s body. To prevent rejection, the immune cells in the womb get an anti-inflammatory or immunosuppressant character. It was previously believed that the mother’s immune system controlled this adjustment itself. But now a study from Linköping University shows that the placenta – which develops from the foetus and is therefore a foreign organ – has an important role in this process.

The study, carried out by a research team led by doctoral student Judit Svensson-Arvelund and Professor Jan Ernerudh has been published in the latest issue of the prestigious Journal of Immunology.

The research group wants to understand how the mother’s immune system is controlled in order to ensure a successful pregnancy, and what factors can lead to complications. Previously the group has shown that particular immune cells - regulatory T cells and macrophages – are important for creating tolerance and preventing excessive inflammation in the womb. However the mechanisms that drive the development of these cells have not been known.

A section of the placenta shown through a microscopeThe new study shows that factors from the placenta can control the development of regulatory T cells and macrophages with anti-inflammatory qualities, and that they can prevent a general activation of the immune system. The researchers identified a number of key molecules, including Interleukin-10 and the growth factor M-CSF.

Hence the placenta has a unique, built-in ability to create immunological tolerance, thus securing the development of the foetus.

The next important step is to analyse whether the identified substances can be used as biomarkers for early detection of pregnancy complications such as miscarriage, pre-eclampsia or prematurity. The group plans to use blood samples from a pregnancy biobank that was started at Kvinnohälsan, a women’s health clinic in Linköping, and that includes more than 4,500 women. The biobank is a collaboration between LiU researchers and Kvinnokliniken, the women’s health clinic at Linköping University Hospital.

”In the longer term we hope the results can make it easier to predict complications and give preventive treatment. This knowledge also provides clues as to how the immune system can be effectively instructed, which cmoderkakaan also be used when treating illnesses with chronic inflammation, such as multiple sclerosis,” says Prof Ernerudh.

The article has been recognised as one of the seven most interesting in the journal’s February issue.

Picture: A specimen from a placenta, where the coloured cells around the perimeter produce the growth factor M-CSF. 

Article: The human fetal placenta promotes tolerance against the semiallogeneic fetus by inducing regulatory T cells and homeostatic M2 macrophages, by J. Svensson-Arvelund, R. B. Mehta, R. Lindau, E. Mirrasekhian, H. Rodriguez-Martinez, G. Berg, G. E. Lash, M. C. Jenmalm and J. Ernerudh. Journal of Immunology 194, 15 February 2015. doi: 10.4049/​jimmunol.1401536