The role of eutopic endometrial CD8+ T cells in adverse reproductive outcomes

 Abstract:

Endometrial mucosa contains both innate and adaptive immune cells, found either as single cells across the stroma and epithelium or as part of lymphoid aggregates. T cells are the most abundant immune population comprising 40–60% of all endometrial leukocytes with > 60% being CD8+ T (CD8 T) cells. Although poorly understood, the endometrial immune milieu is hormonally regulated and may compromise endometrial receptivity leading to adverse reproductive outcomes, such as endometriosis-associated subfertility (EAS) and recurrent pregnancy loss (RPL). Endometriosis is a chronic disease, defined as a growth of endometrium-like tissue outside of the uterus. It affects 1 in 10 women of reproductive age, of which 35–50% suffer from EAS. RPL is defined as the loss of two or more subsequent clinically recognized pregnancies before week 24 and affects 1 in 50 pregnant women.

In my project I aim to determine if the transcriptomic, phenotypic and histological characteristics of CD8 T cells in the endometrium can help us reveal relevant immune modulation in EAS and RPL, which could be detrimental to embryo implantation and pregnancy. Given the invasiveness of endometrial sampling, it is also essential to investigate if dysregulated uterine immunity is mirrored in blood to aid diagnostics and to determine the impact of parity and cycle stage on different CD8 T cell populations for future clinical study design.