KKH and A*STAR scientists discovered that an unborn baby’s immune system is established in the second trimester, and may be working independently of its mother’s.
KKH and A*STAR scientists discovered that an unborn baby’s immune system is established in the second trimester, and may be working independently of its mother’s.
Until recently, the commonly held assumptions about a fetus’s immune system are that it develops only in the later stages of pregnancy, and thus a fetus is largely dependent on the mother’s immune system to defend pathogens.
Scientists from KK Women’s and Children’s Hospital (KKH) and A*STAR’s Singapore Immunology Network (SIgN) have now debunked them.
They found that the early gestation fetus already has a developed immune system as early as the second trimester, or between week 13 and 27 of pregnancy, and that it is able to respond to pathogens as well as foreign proteins (allo-antigens). Their findings were published in Nature on 14 June 2017.
This insight into the beginnings of the human immune system opens possibilities to future immune-directed therapies, and provides better understanding of conditions linked to abnormal immune responses during pregnancy, such as pre-eclampsia.
The scientists studied fetal dendritic cells, which detect and assess threats posed by foreign pathogens to the body, and found that they can already perform key functions found in adults by the second trimester.
The difference is that in the fetus, dendritic cells expresses high levels of Arginase-2, an enzyme that reduces the ability of other immune cells to secrete TNFalpha, a key pro-inflammatory cytokine.
In addition, fetal dendritic cells tend to promote the development of regulatory T-cells, which generates a fetal environment which is largely immune-tolerant, and perhaps prevents the fetal immune system from rejecting the mother’s cells.
Associate Professor Jerry Chan, Senior Consultant, Department of Reproductive Medicine, KKH and joint-senior author of the study, explained the importance:
“We have known for a long time that maternal cells cross into the baby’s blood stream, but are not rejected by the fetal immune system. It had been long thought that the fetal immune system does not reject these semi-foreign cells due to its immaturity.
“The discovery of a fully functional dendritic cell network by the second trimester of pregnancy challenges this belief, and the high expression of Arginase-2 by fetal dendritic cells may contribute to the ability of the fetus to tolerate the mother’s cells.”
This insight opens possibilities to future immune-directed therapies, and provides better understanding of conditions linked to abnormal immune responses during pregnancy, such as pre-eclampsia.
The team is planning to expand their study beyond dendritic cells, to incorporate other key immune cells such as B-cells or T-cells. Dr Florent Ginhoux, Senior Principal Investigator at SIgN, A*STAR, and joint-senior author of the study, said,
“Our eventual goal is to build an atlas of the fetal immune system.”
“Hopefully, this will allow us to discover additional mechanisms of fetal tolerance, and identify gene signatures so that we can better evaluate fetal fitness and immunity.”
