Got your mother in a whirl: The role of maternal T cells and myeloid cells in pregnancy

Abstract

Appropriate development of the placenta is required for healthy pregnancy to occur. After implantation of the fertilized blastocyst, fetal trophoblasts invade the endometrium and myometrium of the mother's uterus to establish placentation. In this process, fetal trophoblasts encounter maternal immune cells. In this review, we focus on the role of maternal T cells and myeloid cells (macrophages, dendritic cells) in pregnancy and their interaction with trophoblasts. To retain immunologic tolerization, trophoblasts evade immune recognition by T cells and produce factors that modulate their phenotype and function. On top of that, the local environment at the maternal‐fetal interface favors expansion of regulatory T cells. Macrophages and dendritic cells are essential in maintaining a healthy pregnancy. They produce soluble factors and act as antigen‐presenting cells, thereby interacting with T cells. Herein, M2 macrophages, immature dendritic cells, CD4+ Th2 cells, and regulatory T cells represent an axis that maintains a local immune tolerant environment. We consider outstanding issues concerning these cell types and their pathways, which need to be addressed in future investigations. Data from recent single‐cell sequencing experiments of the placental bed, to study heterogeneity of maternal immune cells and to predict cell‐cell interactions, are discussed. Novel ways for long‐term culturing of primary trophoblasts allow for cell‐cell interaction studies in a functional way. Future directions should include study of the functionality of currently known and newly identified decidual immune cell subsets in healthy and complicated pregnancies, and their interaction with and modulation by trophoblast cells.

Single‐cell RNA sequencing reveals heterogeneity and differential expression of decidual tissues during the peripartum period

“…Decidual T‐cell numbers change during delivery, perhaps in an effort to maintain homeostasis 46 . Dendritic cells regulate T‐cell responses; T cells interact via a complex web during pregnancy 47 . Decidual immune cells may thus play important roles in pregnancy maintenance and labour onset.…”

Monocytes and macrophages in pregnancy: The good, the bad, and the ugly*

“…127,128 Indeed, innate immune cells at the maternal-fetal interface provide the first line of defense against vertical transmission of viral pathogens. 123 Additionally, placental trophoblasts express a repertoire of PRRs including TLRs (3,7,8,9) and secrete type III interferons leading to the induction of interferon-stimulated genes (ISG). 123,129,130 In vitro analyses show that in response to TLR activation, decidual macrophages secrete both pro-inflammatory and antiinflammatory cytokines.…”

“…Natural killer (NK) and T cells have been widely studied in pregnancy. [3][4][5][6][7][8] In contrast, the adaptations of circulating monocytes and macrophages at the maternal-fetal interface remain poorly defined.…”

Chronic histiocytic intervillositis: A breakdown in immune tolerance comparable to allograft rejection?

“…26 After uNKs, macrophages are the second most abundant decidual leucocyte and persist throughout pregnancy, with the majority polarized towards an M2 anti-inflammatory phenotype. 27 In rodent models, dendritic cells (DCs) are entrapped within the uterus preventing antigen presentation and may be responsible for the induction of Tregs from naïve T cells. 23,28 Stromal cells of the decidua may also contribute towards tolerance via silencing expression of genes related to chemokine production, as shown in mice.…”