Innate Lymphoid Cells at the Maternal-Fetal Interface in Human Pregnancy

Chang, Ruiqi; Zhou, Wen‐Jie; Li, Da‐Jin; Li, Ming‐Qing

doi:10.7150/ijbs.38264

Cited by 16 publications

(8 citation statements)

References 171 publications

(210 reference statements)

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“…This interaction plays a fundamental role in the induction of intestinal commensal bacteria tolerance [49]. Although altered ILCs numbers have been described in disturbed pregnancies, the role of ILCs in fetal tolerance has not been studied extensively yet [50][51][52][53][54][55]. Our group has previously observed that ILCs reduce their antigen presentation potential during pregnancy, and that uterine ILCs retain a low presentation potential [18].…”

Section: Discussionmentioning

confidence: 99%

Oxygen regulates ILC3 antigen presentation potential and pregnancy-related hormone actions

Einenkel

Ehrhardt

Zygmunt

et al. 2022

Reprod Biol Endocrinol

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Early pregnancy is marked by placentation and embryogenesis, which take place under physiological low oxygen concentrations. This oxygen condition is crucial for many aspects of placentation, trophoblast function, vascularization and immune function. Recently, a new family of innate lymphoid cells has been found to be expressed at the fetomaternal interface. Among these, type 3 innate lymphoid cells (ILC3) are important antigen presenting cells in the context of MHC-II. The expression of MHC-II on ILC3s during pregnancy is reduced. We tested the hypothesis that low oxygen concentrations reduce the potential of ILC3s to present antigens promoting fetal tolerance.Using an in vitro approach, NCR+ ILC3s generated from cord blood stem cell precursors were incubated under different O2 concentrations in the presence or absence of the pregnancy-related hormones hCG and TGF-β1. The expression of MHC-II, accessory molecules and an activation marker were assessed by flow cytometry. We observed that 1% O2 reduced the expression of the MHC-II molecule HLA-DR as compared to 21% O2 and modulated the relative effects of hCG and TGF-β1.Our data indicate that low oxygen concentrations reduce the antigen presentation potential of NCR+ ILC3s and suggest that it may promote fetal tolerance during the first trimester of pregnancy.

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Section: Discussionmentioning

confidence: 99%

Oxygen regulates ILC3 antigen presentation potential and pregnancy-related hormone actions

Einenkel

Ehrhardt

Zygmunt

et al. 2022

Reprod Biol Endocrinol

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“…We decided to focus this study on key myeloid and NK populations for pregnancy health and their roles in fetal resorption [26,52,84,88,97,98,100,104], however this does not rule out the importance of other immune populations. T cells, NK-T cells, innate lymphoid cells, and trophoblasts all have roles in pregnancy and may play important roles in LPS-mediated uterine inflammation [1][2][3][105][106][107][108][109][110][111][112][113][114][115][116]. Early stages of uterine blood vessel growth, branching, pruning, and remodeling are control.…”

Section: Discussionmentioning

confidence: 99%

Decidual innate immune cell kinetics following lipopolysaccharide challenge

St-Germain

Castellana

Baltayeva

et al. 2022

Preprint

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In early pregnancy, macrophages (Mϕ) and natural killer cells (NK) infiltrate and expand within the decidua to comprise 30% of all cellular content. These immune cell populations coordinate angiogenic and tissue remodeling processes that are needed for a healthy pregnancy. Importantly, decidual tissue-resident macrophages (trMϕ) and uterine NK retain immunosurveillance properties that facilitate the targeting of infections (e.g., viral, bacterial). The timing and severity of these infections, as well as the resulting immune response, can dictate pregnancy outcome. However, little is known about the kinetics and activities of uterine myeloid and NK populations following infections. To address this knowledge gap, we defined the stepwise changes of uterine myeloid and NK subpopulations following lipopolysaccharide (LPS) challenge in a mouse model of early pregnancy. Low (25 μg/kg), moderate (50 μg/kg), and high (200 μg/kg) doses of LPS resulted in dose-dependent increases in peripheral and uterine inflammation, as well as a dose-dependent increase in the rate of fetal resorption. Compared with saline controls, mice exposed to LPS showed higher frequencies of immature monocytes, decreased TNFα-producing monocytes and Mϕ, and increased conventional (c)NK expression of granzyme B in the uterus. These changes were followed by alterations in overall uterine (u)NK frequencies with increased cNK and decreased tissue resident (tr)NK. Together, this work describes how discrete levels of LPS-induced inflammation shape the innate immune cell landscape of the decidua. These findings establish insight into the stepwise immunological changes following endotoxin challenge and provide a better understanding of how inflammation controls the activity of key decidual leukocytes.

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“…Nevertheless, a second important site of innate immune responses is localized at the decidual layer. The maternal-fetal interface represents the direct contact between the embryo and the mother and it is populated by fetal trophoblast cells, maternal decidual stromal cells (DSCs), and decidual immune cells (DICs) ( 29 ). The decidua is an active site of chemokine synthesis throughout gestation, attracting neutrophils, natural killer cells, dendritic cells, and macrophages ( 17 ).…”

Section: Maternal and Fetal Immune Systemmentioning

confidence: 99%

The Protective Role of Maternal Immunization in Early Life

et al. 2021

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With birth, the newborn is transferred from a quasi-sterile environment to the outside world. At this time, the neonatal immune system is inexperienced and continuously subject to a process of development as it encounters different antigenic stimuli after birth. It is initially characterized by a bias toward T helper 2 phenotype, reduced T helper 1, and cytotoxic responses to microbial stimuli, low levels of memory, and effector T and B cells and a high production of suppressive T regulatory cells. The aim of this setting, during fetal life, is to maintain an anti-inflammatory state and immune-tolerance. Maternal antibodies are transferred during pregnancy through the placenta and, in the first weeks of life of the newborn, they represent a powerful tool for protection. Thus, optimization of vaccination in pregnancy represents an important strategy to reduce the burden of neonatal infections and sepsis. Beneficial effects of maternal immunization are universally recognized, although the optimal timing of vaccination in pregnancy remains to be defined. Interestingly, the dynamic exchange that takes place at the fetal-maternal interface allows the transfer not only of antibodies, but also of maternal antigen presenting cells, probably in order to stimulate the developing fetal immune system in a harmless way. There are still controversial effects related to maternal immunization including the so called “immunology blunting,” i.e., a dampened antibody production following infant's vaccination in those infants who received placentally transferred maternal immunity. However, clinical relevance of this phenomenon is still not clear. This review will provide an overview of the evolution of the immune system in early life and discuss the benefits of maternal vaccination. Current maternal vaccination policies and their rationale will be summarized on the road to promising approaches to enhance immunity in the neonate.

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Innate Lymphoid Cells at the Maternal-Fetal Interface in Human Pregnancy

Cited by 16 publications

References 171 publications

Oxygen regulates ILC3 antigen presentation potential and pregnancy-related hormone actions

Oxygen regulates ILC3 antigen presentation potential and pregnancy-related hormone actions

Decidual innate immune cell kinetics following lipopolysaccharide challenge

The Protective Role of Maternal Immunization in Early Life

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