Abstract
How the semi-allogeneic fetus is tolerated by the maternal immune system remains a fascinating phenomenon. Despite extensive research activity in this field, the mechanisms underlying fetal tolerance are still not well understood. However, there are growing evidences that immune–immune interactions as well as immune–endocrine interactions build up a complex network of immune regulation that ensures fetal survival within the maternal uterus. In the present review, we aim to summarize emerging research data from our and other laboratories on immune modulating properties of pregnancy hormones with a special focus on progesterone, estradiol, and human chorionic gonadotropin. These pregnancy hormones are critically involved in the successful establishment, maintenance, and termination of pregnancy. They suppress detrimental maternal alloresponses while promoting tolerance pathways. This includes the reduction of the antigen-presenting capacity of dendritic cells (DCs), monocytes, and macrophages as well as the blockage of natural killer cells, T and B cells. Pregnancy hormones also support the proliferation of pregnancy supporting uterine killer cells, retain tolerogenic DCs, and efficiently induce regulatory T (Treg) cells. Furthermore, they are involved in the recruitment of mast cells and Treg cells into the fetal–maternal interface contributing to a local accumulation of pregnancy-protective cells. These findings highlight the importance of endocrine factors for the tolerance induction during pregnancy and encourage further research in the field.
Highlights
Endocrine factors modulating immune responses in pregnancyReviewed by: Fulvio D’Acquisto, Queen Mary University of London, UK Stavros Giaglis, University of Basel, Switzerland Ralph Kay Heinrich Nanan, The University of Sydney, Australia
It is said that mammalian pregnancy defies the immunological rules because a semi-allogeneic conceptus is tolerated rather than rejected
Because of the fact that initial allorecognition of foreign fetal antigens by the maternal immune system is advantageous for a successful pregnancy, the mechanisms behind gestational tolerance are of interest for other disciplines
Summary
Reviewed by: Fulvio D’Acquisto, Queen Mary University of London, UK Stavros Giaglis, University of Basel, Switzerland Ralph Kay Heinrich Nanan, The University of Sydney, Australia. We aim to summarize emerging research data from our and other laboratories on immune modulating properties of pregnancy hormones with a special focus on progesterone, estradiol, and human chorionic gonadotropin. These pregnancy hormones are critically involved in the successful establishment, maintenance, and termination of pregnancy. Pregnancy hormones support the proliferation of pregnancy supporting uterine killer cells, retain tolerogenic DCs, and efficiently induce regulatory T (Treg) cells They are involved in the recruitment of mast cells and Treg cells into the fetal–maternal interface contributing to a local accumulation of pregnancy-protective cells.
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