Gene modification helps mouse mum tolerate fetus

Immune rejection, the body's defence mechanism, triggered in response to foreign tissues, is a huge problem for transplant operations. But why does a mother's immune system not reject the developing fetus?

The answer may lie in modifications to genes that usually activate part of the immune response, according to scientists.

A group of proteins called chemokines usually trigger the destruction of foreign tissues, but in this study, published in Science, researchers discovered that in mice they appear to be turned off during pregnancy.

'This is a very exciting finding for us because it gives a satisfying explanation for why the fetus isn't rejected during pregnancy, which is a fundamental question for the medical community with clear implications for human pregnancy', lead researcher Dr Adrian Erlebacher said.

Normally, these chemokines recruit immune cells, called T cells, to the foreign tissue, which destroy it. Dr Erlebacher explained that in during pregnancy this doesn't happen - the specialised membrane in the uterus that surrounds the embryo and placenta, the decidua, is instead a 'zone of relative immunological inactivity'.

They found that the implantation of an embryo causes alterations to the genes that produce the chemokine proteins in decidua cells, in a process called epigenetic silencing. This means that they do not function in the same way, and so do not signal for T cells to attack the developing fetus.

The team, from the New York School of Medicine, is now investigating whether the same mechanisms apply to human pregnancy, and if failures in the process could account for complications such as preterm labour, spontaneous abortion and pre-eclampsia.

It is hoped these findings will also be of use in other fields where immune-tolerance is an important issue, including organ transplantation and autoimmune diseases.