Human chorionic gonadotropin promotes recruitment of regulatory T cells in endometrium by inducing chemokine CCL2

Huang, Xiaomin; Cai, Yunni; Ding, Min; Zheng, Bo; Sun, Haixiang; Zhou, Jianjun

doi:10.1016/j.jri.2019.102856

Cited by 37 publications

(27 citation statements)

References 38 publications

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“…In our study, we found that the expression of Tregs and surface markers are different in peripheral blood before and during pregnancy. It has been suggested that fetus-specific CD4 + Tregs are specifically recruited from PB to the decidua [65,66], and our results showed that the increased proportion of CD4 + Tregs in PB might be involved in the maintenance of pregnancy (at the fetalmaternal interface). Additionally, it is more likely that crucial immunological events occur at the fetalmaternal interface, thus future studies are needed to compare Tregs in both the peripheral blood and the decidua from the same normal pregnant women.…”

Section: Discussionsupporting

confidence: 58%

The Fluctuation of Regulatory T Cells during Pregnancy and Obstetrical Complications

Zhao

Bao

et al. 2020

Preprint

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Background: Regulatory T cells (Tregs) are critical immunomodulators during pregnancy by preventing maternal T-cell activation against fetal cells. However, how characteristics of maternal Tregs vary during pregnancy is still unclear. We analyzed the proportion and phenotypic characteristics of peripheral blood Tregs in normal pregnant women, women with recurrent pregnancy loss (RPL) or gestational diabetes mellitus (GDM), and non-pregnant women.Methods: We investigated the proportion of CD4+ Tregs, CD8+ Tregs and the expression of PD-1, GITR, HLA-G and CTLA-4 on them in the peripheral blood of normal pregnancies during 1st (n = 28), 2nd (n = 43), and 3rd trimester (n = 33); In addition, we evaluated pregnancies in the 1st trimester complicated by RPL (n = 21), in the 2nd (n = 17) and 3rd trimester (n = 28) complicated by GDM. Non-pregnant women (n = 57) were also investigated using flow cytometry.Results: During normal pregnancy, the proportion of CD4+ Tregs in all trimester and CD8+ Tregs in 2nd and 3rd trimester were higher(P ＜ 0.05，respectively) compared with non-pregnancy women. Moreover, the proportion of CD4+ Tregs was higher in 2nd trimester compared to 1st and 3rd trimester (P ＜ 0.01) while the proportion of CD8+ Tregs was higher in 3rd trimester compared to 1st and 2nd trimester (P ＜ 0.05). Compared to non-pregnant studies, the proportion of GITR+/CD8+ Tregs and HLA-G+/CD8+ Tregs in all trimester were higher(P ＜ 0.05, respectively). Moreover, the proportion of PD-1+/CD4+ Tregs, GITR+/CD4+ Tregs, PD-1+/CD8+ Tregs and CTLA-4+/CD8+ Tregs in 3rd trimester were significantly higher compared to 1st, 2nd trimester and non-pregnant group(P ＜ 0.05, respectively).In RPL and GDM groups, the proportions of CD4+ Tregs in all trimesters were decreased while the proportions of CD8+ Tregs in all trimesters were increased compared to normal pregnant group (P ＜ 0.05，respectively).In RPL group, the proportion of PD-1+/CD4+ Tregs, GITR+/CD4+ Tregs and HLA-G+/CD4+ Tregs were decreased compared to 1st trimester normal pregnant group (P ＜ 0.05，respectively). In 2nd trimester GDM group, the proportion of HLA-G+/CD4+ Tregs were decreased compared to 2nd trimester normal pregnant group (P ＜ 0.05，respectively). In 3rd trimester GDM group, the proportion of PD-1+/CD4+ Tregs, GITR+/CD4+ Tregs, PD-1+/CD8+ Tregs, GITR+/CD8+ Tregs and HLA-G+/CD8+Tregs were decreased compared to 3rd trimester normal pregnant group (P ＜ 0.05, respectively).Conclusions: The proportion of CD4+ Tregs and CD8+ Tregs increased during pregnancy, the proportions and subsets of CD4+ Tregs decreased and those of CD8+ Tregs increased in pregnancies complicated by RPL and GDM, indicating that regulatory T cells play a role in pregnancy maintenance, and the abnormal expression of Tregs might be related to the complicated pregnancy.

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Section: Discussionsupporting

confidence: 58%

The Fluctuation of Regulatory T Cells during Pregnancy and Obstetrical Complications

Zhao

Bao

et al. 2020

Preprint

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“…Specifically, chemokine receptor expressions (especially CCR molecules) on CD4 + T cells determine their trafficking patterns, including the target tissue, timing, and signals to receive (29). Once T cells are recruited to the uterine lining, these cells are induced to display unique phenotypic properties by the micromilieu of the maternal-fetal interface (30,31). Quickly after the placental implantation, the Th2 shift is seemingly noticeable, which is critical for the maintenance and development of normal fetus and placenta (32), and as well as suppression of Th1 immunity at the maternal-fetal junction (2,9,13,33).…”

Section: Th1 Immunity For Controlled Inflammation During Implantationmentioning

confidence: 99%

T Helper (Th) Cell Profiles in Pregnancy and Recurrent Pregnancy Losses: Th1/Th2/Th9/Th17/Th22/Tfh Cells

et al. 2020

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During pregnancy, various immune effectors and molecules participating in the immunemicroenvironment establish specific maternal tolerance toward the semi-allogeneic fetus. Activated maternal immune effectors by the trophoblast antigens, such as T helper (Th), T cytotoxic (Tc), T regulatory (Treg), and B cells, are involved in the regulation of adaptive immunity. Recognition of active signal through the T cell receptors stimulate the differentiation of naive CD3 + CD4 + T cells into specific T cell subsets, such as Th1, Th2, Th9, Th17, Th22, and follicular Th cells (Tfh). Each of these subsets has a significant and distinct role in human pregnancy. Th1 immunity, characterized by immune-inflammatory responses, becomes dominant during the peri-implantation period, and the "controlled" Th1 immunity benefits the invading trophoblasts rather than harm. Quickly after the placental implantation, the early inflammatory Th1 immunity is shifted to the Th2 antiinflammatory immune responses. The predominant Th2 immunity, which overrules the Th1 immunity at the placental implantation site, protects a fetus by balancing Th1 immunity and accommodate fetal and placental development. Moreover, Treg and Th9 cells regulate local inflammatory immune responses, potentially detrimental to the fetus. Th17 cells induce protective immunity against extracellular microbes during pregnancy. However, excessive Th17 immunity may induce uncontrolled neutrophil infiltration at the maternal-fetal interface. Other Th cell subsets such as Tfh cells, also contribute to pregnancy by setting up favorable humoral immunity during pregnancy. However, dysregulation of Th cell immunity during pregnancy may result in obstetrical complications, such as recurrent pregnancy losses (RPL) and preeclampsia (PE). With this review, we intend to deliver a comprehensive overview of CD4 + Th cell subsets, including Th1, Th2, Th9, Th17, Th22, and Tfh cells, in human pregnancy by reviewing their roles in normal and pathological pregnancies.

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“…The impact of using hCG on immunological mechanisms during embryonic implantation is unknown. Studies have shown that hCG increases endometrial levels of proangiogenic factors (VEGF and insulin‐like growth factor II), modulates the proliferation of uNKs, and raises levels of Tregs and CD4 + /CD25 + /Foxp3 + , and trophoblastic invasion 51‐53 …”

Section: Discussionmentioning

confidence: 99%

Intrauterine perfusion immunotherapies in recurrent implantation failures: Systematic review

Cavalcante

Sarno

et al. 2020

American J Rep Immunol

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Studies have investigated the gestational outcomes of new immunological therapies in the treatment of patients with recurrent implantation failure (RIF) in assisted reproductive technology (ART). The objective of this article is to assess the current state of evidence available in the literature on intrauterine perfusion immunotherapies in women undergoing ART treatments. By considering the guidelines of Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA), the authors performed systematic review by searching the databases of PubMed/MEDLINE and Scopus using the following key words: “recurrent implantation failure,” “intrauterine infusion,” “Platelet‐Rich Plasma (PRP),” “Peripheral Blood Mononuclear Cells (PBMC),” “Granulocyte Colony‐Stimulating Factor (G‐CSF),” and “Human Chorionic Gonadotropin (hCG).” The authors analyzed the indications and the impact of new immunological therapies with intrauterine infusions on the pregnancy outcomes of patients undergoing ART. PRP, PBMC, G‐CSF, and hCG were the four most used immunological therapies with intrauterine infusion. These new therapies appear to improve the results of ART treatments in cases of RIF. However, the small number of studies does not allow definitive conclusions about the effectiveness of these therapies.

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Human chorionic gonadotropin promotes recruitment of regulatory T cells in endometrium by inducing chemokine CCL2

Cited by 37 publications

References 38 publications

The Fluctuation of Regulatory T Cells during Pregnancy and Obstetrical Complications

The Fluctuation of Regulatory T Cells during Pregnancy and Obstetrical Complications

T Helper (Th) Cell Profiles in Pregnancy and Recurrent Pregnancy Losses: Th1/Th2/Th9/Th17/Th22/Tfh Cells

Intrauterine perfusion immunotherapies in recurrent implantation failures: Systematic review

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