New Paradigm in the Role of Regulatory T Cells During Pregnancy

Tsuda, S.; Nakashima, Akitoshi; Saito, Tomoko; Saito, Shigeru

doi:10.3389/fimmu.2019.00573

Cited by 143 publications

(115 citation statements)

References 109 publications

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“…The observed increase in activated CD4+ T cells may be counteracted by an increase in Treg in term parietalis to secure success of pregnancy. Evidently, functional assays are necessary to further explore the co-existence of effector memory CD4+ T cells with nTreg and iTreg, especially in the context of complicated pregnancies (54). Treg may also be essential in the regulation of distinct CD4+ and CD8+ NKTlike clusters in early pregnancy, as suggested by the increased percentages of NKT cells observed in women with unexplained recurrent spontaneous abortions (55).…”

Section: Discussionmentioning

confidence: 99%

Visualizing Dynamic Changes at the Maternal-Fetal Interface Throughout Human Pregnancy by Mass Cytometry

et al. 2020

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During healthy pregnancy, a balanced microenvironment at the maternal-fetal interface with coordinated interaction between various immune cells is necessary to maintain immunological tolerance. While specific decidual immune cell subsets have been investigated, a system-wide unbiased approach is lacking. Here, mass cytometry was applied for data-driven, in-depth immune profiling of the total leukocyte population isolated from first, second, and third trimester decidua, as well as maternal peripheral blood at time of delivery. The maternal-fetal interface showed a unique composition of immune cells, different from peripheral blood, with significant differences between early and term pregnancy samples. Profiling revealed substantial heterogeneity in the decidual lymphoid and myeloid cell lineages that shape gestational-specific immune networks and putative differentiation trajectories over time during gestation. Uncovering the overall complexity at the maternal-fetal interface throughout pregnancy resulted in a human atlas that may serve as a foundation upon which comprehension of the immune microenvironment and alterations thereof in pregnancy complications can be built.

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Section: Discussionmentioning

confidence: 99%

Visualizing Dynamic Changes at the Maternal-Fetal Interface Throughout Human Pregnancy by Mass Cytometry

et al. 2020

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“…Therefore, the reduced KIR2DL4 expression levels on decidual NK cells have been thought to increase the susceptibility of NK cell-mediated cytotoxic activity and the following recurrent spontaneous abortion [63]. Regulatory T cells (Tregs) have also been also implicated in the establishment of pregnancy [64]. Reduced numbers of decidual Tregs were observed in some women with recurrent spontaneous abortion [65][66][67].…”

Section: Involvement Of Kir2dl4 On Human Mast Cells In the Establishmmentioning

confidence: 99%

Killer Immunoglobulin-Like Receptor 2DL4 (CD158d) Regulates Human Mast Cells both Positively and Negatively: Possible Roles in Pregnancy and Cancer Metastasis

Kataoka

Ueshima

Hirata

et al. 2020

IJMS

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Killer immunoglobulin-like receptor (KIR) 2DL4 (CD158d) was previously thought to be a human NK cell-specific protein. Mast cells are involved in allergic reactions via their KIT-mediated and FcɛRI-mediated responses. We recently detected the expression of KIR2DL4 in human cultured mast cells established from peripheral blood of healthy volunteers (PB-mast), in the human mast cell line LAD2, and in human tissue mast cells. Agonistic antibodies against KIR2DL4 negatively regulate the KIT-mediated and FcɛRI-mediated responses of PB-mast and LAD2 cells. In addition, agonistic antibodies and human leukocyte antigen (HLA)-G, a natural ligand for KIR2DL4, induce the secretion of leukemia inhibitory factor and serine proteases from human mast cells, which have been implicated in pregnancy establishment and cancer metastasis. Therefore, KIR2DL4 stimulation with agonistic antibodies and recombinant HLA-G protein may enhance both processes, in addition to suppressing mast-cell-mediated allergic reactions.

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“…Transforming growth factor‐beta superfamily members are closely associated with tissue remodeling events and reproductive processes. Embryonic trophoblasts, maternal DSCs, and decidual lymphocytes constituting the maternal‐fetal interface produce substantial TGF‐β 70‐73 74‐76 .…”

Section: Discussionmentioning

confidence: 99%

Tissue‐resident CD8⁺T memory cells with unique properties are present in human decidua during early pregnancy

Huang

Liu

et al. 2020

American J Rep Immunol

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Problem Resident memory T (TRM) cells reside in the uterus during pregnancy may play an important role in balancing maternal‐fetal tolerance with anti‐infectious immunity. Although CD8+TRM and decidual CD8+T cells have been extensively characterized, the properties of decidual CD8+TRM (dTRM) cells remain poorly defined. Method of study We investigated the heterogeneity, phenotypes, and functions of dTRM cells, and compared the proportion of dTRM cells between normal pregnancy and recurrent spontaneous abortion (RSA) using flow cytometry. Moreover, we cocultured peripheral CD8+T (CD8+pT) cells with trophoblast, or decidual stomal cells (DSCs) in the presence or absence of anti‐TGF‐β antibody or TGF‐β type I receptor inhibitor to explore the effects of maternal‐fetal environment on decidual CD8+TRM cell formation. Results We found that CD69+CD103+TRM cells were abundant in CD8+dT cells but not in CD4+dT cells with effector‐memory (EM, CD45RA−CCR7−) phenotypes. The percentage of dTRM cells from RSA patients was significantly higher than that from normal pregnancy. Furthermore, dTRM cells showed increased expressions of chemokine receptors, T‐cell exhaustion‐related molecules, and produced more anti‐inflammatory cytokines and effector cytokines upon stimulation. Moreover, DSCs produced a considerable level of TGF‐β and upregulated CD103 expression on CD69+CD8+pT cells, which can be significantly reversed by blocking TGF‐β receptor. Conclusion Our findings demonstrate that TRM cells with unique properties are present in the decidua during human early pregnancy. They possess an enhanced capacity to produce effector cytokines and regulatory molecules, which might be important in the balance between maternal‐fetal immune tolerance and the capacity to aggressively respond to infections.

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New Paradigm in the Role of Regulatory T Cells During Pregnancy

Cited by 143 publications

References 109 publications

Visualizing Dynamic Changes at the Maternal-Fetal Interface Throughout Human Pregnancy by Mass Cytometry

Visualizing Dynamic Changes at the Maternal-Fetal Interface Throughout Human Pregnancy by Mass Cytometry

Killer Immunoglobulin-Like Receptor 2DL4 (CD158d) Regulates Human Mast Cells both Positively and Negatively: Possible Roles in Pregnancy and Cancer Metastasis

Tissue‐resident CD8⁺T memory cells with unique properties are present in human decidua during early pregnancy

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New Paradigm in the Role of Regulatory T Cells During Pregnancy

Cited by 143 publications

References 109 publications

Visualizing Dynamic Changes at the Maternal-Fetal Interface Throughout Human Pregnancy by Mass Cytometry

Visualizing Dynamic Changes at the Maternal-Fetal Interface Throughout Human Pregnancy by Mass Cytometry

Killer Immunoglobulin-Like Receptor 2DL4 (CD158d) Regulates Human Mast Cells both Positively and Negatively: Possible Roles in Pregnancy and Cancer Metastasis

Tissue‐resident CD8+T memory cells with unique properties are present in human decidua during early pregnancy

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Tissue‐resident CD8⁺T memory cells with unique properties are present in human decidua during early pregnancy