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Regulatory T cells in embryo implantation and the immune response to pregnancy
Sarah A. Robertson, … , Alison S. Care, Lachlan M. Moldenhauer
Sarah A. Robertson, … , Alison S. Care, Lachlan M. Moldenhauer
Published October 1, 2018
Citation Information: J Clin Invest. 2018;128(10):4224-4235. https://doi.org/10.1172/JCI122182.
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Review

Regulatory T cells in embryo implantation and the immune response to pregnancy

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Abstract

At implantation, the embryo expresses paternally derived alloantigens and evokes inflammation that can threaten reproductive success. To ensure a robust placenta and sustainable pregnancy, an active state of maternal immune tolerance mediated by CD4+ regulatory T cells (Tregs) is essential. Tregs operate to inhibit effector immunity, contain inflammation, and support maternal vascular adaptations, thereby facilitating trophoblast invasion and placental access to the maternal blood supply. Insufficient Treg numbers or inadequate functional competence are implicated in idiopathic infertility and recurrent miscarriage as well as later-onset pregnancy complications stemming from placental insufficiency, including preeclampsia and fetal growth restriction. In this Review, we summarize the mechanisms acting in the conception environment to drive the Treg response and discuss prospects for targeting the T cell compartment to alleviate immune-based reproductive disorders.

Authors

Sarah A. Robertson, Alison S. Care, Lachlan M. Moldenhauer

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Figure 1

Tregs are critical for controlling inflammation in the transition to an antiinflammatory decidual environment necessary for embryo implantation and progression of pregnancy.

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Tregs are critical for controlling inflammation in the transition to an ...
Mouse models show that Tregs act to suppress inflammation, prevent adverse effects of antifetal alloantigen Teff cells, and allow vascular adaptations required for placental morphogenesis (39, 41, 62, 63, 82, 87). Tregs arise as a consequence of events during the inflammation-like response in the periconception phase, and their abundance, suppressive function, and stability are impacted by events at conception and in the preimplantation phase (39, 83–85, 135, 137). Tregs sustain an antiinflammatory environment until a decline, associated with the inflammation events of parturition and birth, is triggered (40, 64, 88, 89). Decidual Tregs in pregnant women show kinetics and regulatory mechanisms comparable to those in mice (36, 52–54, 56, 58, 59). Recurrent implantation failure, recurrent miscarriage, preeclampsia, and in utero growth restriction are all linked with insufficient numbers, reduced suppressive function and/or instability of Tregs (19–21, 23, 24), and excessive inflammation in the uterus and/or gestational tissues (21, 27, 80).

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