Prenatal immune system more mature than previously thought

22 January 2019• PRESSRELEASE

Contrary to previous assumptions, the womb is probably not a sterile environment. Researchers from the LUMC, together with colleagues from Delft in the Netherlands as well as British and Russian scientists, have found relatively mature immune cells in the intestines of foetuses. This indicates exposure to bacteria in the womb. They have published their findings in Nature Immunology.

PhD students Na Li and Vincent van Unen isolated what are called T cells from the intestines of foetuses and analysed their appearance, behaviour and degree of maturity. “The great thing is that whichever way we looked at them, all the results pointed in the same direction: the T cells are already fairly mature. They looked like mature cells and behaved that way too,” explains Van Unen. T cells start their lives as naive cells and then gradually develop into mature and active cells, once they have come into contact with bacteria or viruses.

The researchers also found this development in the foetal intestines. Using a technique that they developed together with Delft Technical University, they were able to examine individual cells. Van Unen: “The tool allows us to simulate the cells’ development over time. We saw naive cells, mature cells and all stages in between. This reinforced our view that the development of T cells actually takes place in the intestines.”

Preparation for the outside world

The researchers suspect that the mature T cells have reacted to bacterial components in the amniotic fluid. These probably come from the mother’s microbiome. The embryo drinks the amniotic fluid, so that the bacterial components find their way into its intestines and encounter immune cells there. “This is a safe way for the child’s immune system to prepare for the outside world, which is of course swarming with bacteria,” says study director Professor Frits Koning.

Auto-immune diseases

This early ‘training’ of the immune system may, however, also have drawbacks. Koning: “It is admittedly speculation, but we know that the probability of developing immune-mediated diseases and allergies depends to a great extent on environmental factors. If the child’s immune system really is influenced by the mother’s microbiome, that might partly explain why some children develop an allergy or an auto-immune disease and others do not."

The study is financed partly by a grant from the China Scholarship Council.
Would you like to know more? You can read the article ‘Memory CD4+ T cells are generated in the human fetal intestine’ on the Nature Immunology website.

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