New thesis explores the local environment of the uterus
Corinna Mayer from the Center for Infectious Medicine (CIM) at the Department of Medicine, Huddinge (MedH), will defend her thesis entitled "Plasticity of the human uterine immune microenvironment" on 23 October. Her supervisor is Niklas Björkström.
What is the main focus of your thesis?
My thesis explores how the local environment of the uterus shapes its immune cells. The uterus is a highly dynamic organ: its inner lining, the endometrium, is shed, repaired and rebuilt during every menstrual cycle and changes even further during pregnancy. Immune cells are part of all of these processes.
A central idea of my thesis is that the identity of uterine immune cells is not fixed. Instead, their characteristics and functions are continuously shaped by signals from the surrounding tissue. I studied this from three different perspectives: how local signals influence uterine natural killer (NK) cells, how the immune system of the uterus is rebuilt after transplantation, and how immune cells change in their phenotype, location and metabolism across the menstrual cycle.
Which are the most important results?
One of the main findings is that the uterine environment can actively shape incoming immune cells and give them characteristics that are typical of the uterus.
We found that local signals such as IL-15 and TGF-β can change the receptor profile of NK cells and promote features characteristic of uterine NK cells. After uterus or stem cell transplantation, newly arriving immune cells were also able to acquire uterine characteristics and recreate the spatial organization normally seen in the endometrium.
Finally, we found that the healthy endometrial immune environment changes substantially across the menstrual cycle. Immune cells changed not only in number, but also in their phenotype, metabolism and position within the tissue. Together, these findings show that uterine immunity is highly adaptable and closely connected to the surrounding tissue environment.
How can this new knowledge contribute to the improvement of people’s health?
To understand what goes wrong in disease, we first need a detailed understanding of what is normal. My work provides a reference for how immune cells are organized and how they change during the menstrual cycle in healthy women. Our results also show that simply measuring how many immune cells are present may not be enough. Their phenotype, metabolism, location within the tissue and the phase of the menstrual cycle also matter. In the longer term, a better understanding of normal uterine immunity may help us identify which changes are associated with disease and which are part of normal physiological variation.
What are your future ambitions?
I feel very fortunate to have found reproductive immunology, which is a relatively small field but one that I find incredibly interesting. There are still many fundamental questions about how the immune system contributes to reproductive health, and I would very much like to continue working in this area.
My PhD has given me a broad methodological toolbox, but perhaps even more importantly, it has taught me how to think critically about scientific questions and how to approach complex biological systems. I hope to use that experience in future research and to contribute to a better understanding of reproductive biology and women’s health.
Thesis defence
Friday 23 October, 09:30, Erna Möller in Neo, Blickagången 16, Flemingsberg