bims-reprim 2021-02-28 papers

Issue of 2021–02–28
two papers selected by
Iva Filipovic, Karolinska Institutet

Sci Immunol. 2021 Feb 19. pii: eabb7800. [Epub ahead of print]6(56):

Continuous human uterine NK cell differentiation in response to endometrial regeneration and pregnancy.

Benedikt Strunz, Jonna Bister, Hanna Jönsson, Iva Filipovic, Ylva Crona-Guterstam, Egle Kvedaraite, Natalie Sleiers, Bogdan Dumitrescu, Mats Brännström, Antonio Lentini, Björn Reinius, Martin Cornillet, Tim Willinger, Sebastian Gidlöf, Russell S Hamilton, Martin A Ivarsson, Niklas K Björkström.

Immune cell differentiation is critical for adequate tissue-specific immune responses to occur. Here, we studied differentiation of human uterine natural killer cells (uNK cells). These cells reside in a tissue undergoing constant regeneration and represent the major leukocyte population at the maternal-fetal interface. However, their physiological response during the menstrual cycle and in pregnancy remains elusive. By surface proteome and transcriptome analysis as well as using humanized mice, we identify a differentiation pathway of uNK cells in vitro and in vivo with sequential acquisition of killer cell immunoglobulin-like receptors and CD39. uNK cell differentiation occurred continuously in response to the endometrial regeneration and was driven by interleukin-15. Differentiated uNK cells displayed reduced proliferative capacity and immunomodulatory function including enhanced angiogenic capacity. By studying human uterus transplantation and monozygotic twins, we found that the uNK cell niche could be replenished from circulation and that it was under genetic control. Together, our study uncovers a continuous differentiation pathway of human NK cells in the uterus that is coupled to profound functional changes in response to local tissue regeneration and pregnancy.

DOI: https://doi.org/10.1126/sciimmunol.abb7800

Reproduction. 2021 Feb 01. pii: REP-20-0428.R1. [Epub ahead of print]

Investigation of infertility using endometrial organoids.

Konstantina Nikolakopoulou, Margherita Y Turco.

Infertility is a common problem in modern societies with significant socio-psychological implications for women. Therapeutic interventions are often needed which, depending on the cause, can be either medical treatment, surgical procedures or assisted reproductive technology (ART). However, the treatment of infertility is not always successful due to our limited understanding of the preparation of the lining of the uterus, the endometrium, for pregnancy. The endometrium is of central importance for successful reproduction as it is the site of placental implantation providing the interface between the mother and baby. Due to the dynamic, structural and functional changes the endometrium undergoes throughout the menstrual cycle, it is challenging to study. A major advance is the establishment of 3D organoid models of the human endometrium to study this dynamic tissue in health and disease. In this review, we describe the changes that the human endometrium undergoes through the different phases of the menstrual cycle in preparation for pregnancy. We discuss defects in the processes of endometrial repair, decidualization and acquisition of receptivity that are associated with infertility. Organoids could be utilised to investigate the underlying cellular and molecular mechanisms occurring in non-pregnant endometrium and early pregnancy. These studies may lead to therapeutic applications that could transform the treatment of reproductive failure.

DOI: https://doi.org/10.1530/REP-20-0428