Understanding the role of the mother’s immune system in preterm birth
Research institute:
Imperial College London
Project dates:
Grant Awarded: 10 Oct 2018
Funding awarded:
Grant Amount: £111,808.14
We don’t know enough about how the mother’s immune system is involved in early pregnancy and the consequences this has on preterm birth. Dr Antonia Cuff studied the role of cells called ILC3s in early pregnancy. Her research has contributed to knowledge which may one day prevent babies being born too soon.
The challenge
For many women who give birth prematurely, we can’t explain to them why it happened. Scientists believe that the mother’s immune system plays a key role, even from early pregnancy. But we simply don’t know enough about how the immune system is involved in normal pregnancy, and what goes wrong in pregnancies that end in preterm labour or other complications.
We need to better understand the role of the mother’s immune system in pregnancy, so that we can ensure more babies are born healthy and at the right time.
The project
Dr Antonia Cuff did her PhD research under the supervision of Dr Viki Male. In her PhD project, Dr Cuff was studying a type of immune cell call ‘group 3 innate lymphoid cells’, or ILC3s for short.
Drs Cuff and Male thought that ILC3s could have an important role to play in pregnancy and labour. This is because ILC3s produce a molecule called IL-22, which previous research in mice has shown may prevent labour. This prompted Dr Cuff to study whether ILC3s have the same effects in humans.
In this project, which ended in 2024, Dr Cuff examined samples from preterm and full-term pregnancies, assessing the number and activity of ILC3s in these samples. She found that ILC3s didn’t respond to bacterial infections in human pregnancies, like they do in mice. But Dr Cuff did find that ILC3s are active in repairing the womb, either after a period or after giving birth.
She also found that ILC3s were not working effectively in the womb samples donated by women with endometriosis. This condition can cause abnormal periods, chronic pelvic pain, and sometimes infertility. Having endometriosis also makes it more likely that women will give birth prematurely.
What difference will this project make?
Dr Cuff’s research on ILC3s in the womb has contributed to our understanding of how the mother’s immune system may be involved in preterm birth.
Further research in this area could help develop tests to predict if a woman is likely to go into preterm labour. This would allow doctors to intervene early to prevent them giving birth too soon.
Ultimately, this would mean that more babies would be born healthy, giving them the best possible start to their life.
Nurturing Talent
One of Borne’s objectives is to build and strengthen the UK’s preterm birth research community. This will help speed up discoveries that will stop babies being born too soon. One of the ways we do this is by supporting the training of new scientists through funding PhD studentships.
Dr Antonia Cuff was one of several PhD students funded by Borne under the supervision of Dr Viki Male. Dr Antonia Cuff explains what her PhD studentship meant to her:
“My PhD project looking at the dynamics of ILC3 frequencies and numbers in the uterus led to an exploration of a women’s health problem of abnormal menstruation called endometriosis, in which chronic pelvic pain and infertility persist. This experience allowed me to acquire my first Postdoctoral role to study the aetiology of Endometriosis and locate novel tools for its diagnosis and treatment in the team of Prof Erin Greaves at the University of Warwick.
“My PhD presented elements of genomic research in the form of bulk RNA sequencing experiments which was a starting point in my understanding. By collaborating on projects with other Borne-funded students, I began to appreciate the integration of both computational and laboratory disciplines to address research questions, such as the analyses of immune cell dynamics across different reproductive tissues. The projects I worked on during my PhD inspired me to propose using a blend of computational and laboratory tools when I developed my current research project, and was recently awarded a competitive Postdoctoral fellowship for Black scholars at the Wellcome Sanger Institute, which is renowned for their expertise in genomics research. Working with haematologist Dr Jyoti Nangalia, I am studying the appearance of cancer-driver mutations and determining their developmental trajectory over a person’s lifetime.
“Separately from the experimental work, my PhD provided opportunities to communicate science in different formats. I won competitive travel awards enabling me to present our team’s research at international conferences, supervised projects and even collaborated on a project with teams at the University of Edinburgh, both enhancing my network and making connections for future collaborative projects.
“A PhD is an exploration of a complex topic, with the opportunity to design new strategies to answer questions that advance understanding and communicate findings allowing others to build upon them. In this manner, we collectively move closer to solving the health problems of our society. Thank you Dr Viki Male and Borne. What an amazing opportunity it was to have studied for my PhD with you! I appreciated your support of my PhD and I hope to pass it forward.”
