Study shows how the fetal environment may reduce the risk of type 1 diabetes

Professor Kristina Lejon and research engineer Emma Renman show that the environment in the womb can shape immune system development and help reduce the risk of type 1 diabetes, independent of genetic factors. 

ImageJohanna Nordström

“Our results from a mouse study suggest that the maternal immune system influences how the offspring’s immune cells mature and function, beyond what genetics alone can explain,” says Kristina Lejon, Professor at the Department of Clinical Microbiology at Umeå University, who led the study.

The study is based on a well-established experimental model using mice that spontaneously develop type 1 diabetes, known as NOD mice. The researchers transferred NOD embryos into females of another mouse strain (B6). This approach allowed them to investigate how the fetal environment – independent of genetics – affects immune system development and the subsequent risk of disease.

NOD mice that developed in B6 females showed around a 50 percent lower incidence of type 1 diabetes compared with NOD mice carried by NOD females. At the same time, the degree of inflammatory infiltration in the pancreas was comparable between the groups, suggesting that the difference lies in how the immune response is regulated rather than whether inflammation occurs.

When the researchers examined the immune systems of these mice, they observed long-lasting changes. The immune system appeared more balanced, with an increased number of cells that dampen excessive immune responses and altered patterns of self-reactive antibodies. This in turn may reduce the likelihood of disease development.

The researchers were able to rule out genetic differences and postnatal influences from the maternal gut microbiota as explanations for the effect.

“One possible explanation is instead that antibodies transferred via the placenta influence how the immune system is programmed early in life,” says Emma Renman, research engineer at the Department of Clinical Microbiology at Umeå University.

“This shows that maternal factors can shape the offspring’s immune system in a deeper way than previously understood,” says Kristina Lejon.

The study raises new questions about whether similar mechanisms may influence disease risk in humans, and how early factors during pregnancy could potentially contribute to preventing autoimmune disease.

The study was conducted at Umeå University and funded by the Odd Fellow Order and Umeå University.