Programmed cell death-1 (PD-1) and T-cell immunoglobulin mucin-3 (Tim-3) regulate CD4<sup>+</sup>T cells to induce Type 2 helper T cell (Th2) bias at the maternal–fetal interface

Wang, Songcun; Zhu, Xiao‐Yong; Xu, Yuanyuan; Zhang, Di; Li, Yanhong; Yu, Tao; Piao, Hailan; Li, Da‐Jin; Du, Meirong

doi:10.1093/humrep/dew019

Cited by 91 publications

(87 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…More importantly, recent studies have revealed that SGK1 selectively differentiated T H 1 and T H 2 CD4 + T cells 36. Such observations are of great importance to embryo implantation and the subsequent maintenance of pregnancy, as the feto-maternal interface predominantly favors a T H 2 type of intrauterine immunity 37. Therefore, we wondered whether E 2 -activated SGK1 affected the production of pro-inflammatory and T H 1 cytokines in LPS-challenged DSCs as well as the transduction pathways involved.…”

Section: Resultsmentioning

confidence: 96%

“…SGK1 was found to facilitate T H 2 differentiation by phosphorylating Nedd4-2 to inhibit degradation of the transcription factor JunB under the T H 2-polarizing conditions, while suppressing the generation of T H 1 cytokines 36. These findings are of particular importance to the maintenance of gestation, as the feto-maternal interface primarily favors a T H 2 shift 37.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Estradiol Suppresses TLR4-triggered Apoptosis of Decidual Stromal Cells and Drives an Anti-inflammatory T_H2 Shift by Activating SGK1

Lou¹,

Hu²,

Wang³

et al. 2017

Int. J. Biol. Sci.

View full text Add to dashboard Cite

A pro-inflammatory cytokine profile at the feto-maternal interface may predispose immune maladaptation notably in early miscarriages. We investigated the involvement of estradiol (E2)-activated serum-glucocorticoid regulated kinase 1 (SGK1) in preserving the tolerogenic and pro-survival intrauterine microenvironment beneficial to gestation maintenance. Decidual SGK1 was down-regulated in early miscarriage, consistent with the lower serum E2 concentration seen in pregnancy loss. Lipopolysaccharide (LPS)/Toll-like receptors 4 (TLR4) signaling induced apoptosis and the pro-inflammatory T helper type (TH) 1 response of decidual stromal cells (DSCs) were associated with miscarriage. SGK1 activation was suppressed by LPS/TLR4 signaling and would be rescued by E2 administration via the PI3K signaling pathway in DSCs. SGK1 activation attenuated TLR4-mediated cell apoptosis, while promoting cell viability of DSCs by up-regulating the pro-survival genes BCL2 and XIAP, and enhancing the phosphorylation of FOXO1. Furthermore, E2-induced SGK1 activation reduced the secretion of pro-inflammatory TH1 cytokines, and promoted the generation of TH2 cytokines and elevated IRF4 mRNA and protein levels in LPS-incubated DSCs. Pharmacologic inhibition of SGK1 or suppression by small interfering (si) RNA increased the phosphorylation and nuclear translocation of NF-κB to reverse the pro-TH2 and anti-inflammatory effects of E2 pretreatment, leading to compromised pregnancy. These findings suggest that the E2-mediated SGK1 activation suppressed LPS-mediated apoptosis and promoted the anti-inflammatory TH2 responses in DSCs, ultimately contributing to a successful pregnancy.

show abstract

Section: Resultsmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Estradiol Suppresses TLR4-triggered Apoptosis of Decidual Stromal Cells and Drives an Anti-inflammatory T_H2 Shift by Activating SGK1

Lou¹,

Hu²,

Wang³

et al. 2017

Int. J. Biol. Sci.

View full text Add to dashboard Cite

show abstract

“…More than 20 years ago, Saito and colleagues observed that in the first trimester of human normal pregnancy, decidual CD4 + T (dCD4 T) cells express the T-cell-activation antigens CD69, HLA-DR, interleukin-2 receptor-alpha (IL-2Rα), and IL-2Rβ at a significantly higher level than do peripheral blood CD4 + T (pCD4 T) cells, indicating that dCD4 T cells are regionally activated at an early stage of pregnancy (17). Furthermore, recent studies showed that dCD4 T cells in early pregnancy express higher levels of the T regulatory (Treg)-cell markers CD25 and FOXP3, the proliferation-associated antigen Ki-67, programmed cell death-1 (PDCD1, also called PD-1), and T-cell immunoglobulin mucin-3 (Tim-3) than their peripheral blood counterparts (13, 18–20). However, the complexity of dCD4 T cells has not been well elucidated, and a thorough understanding of the molecular and functional features of these cells would shed light on their eventual roles during early pregnancy.…”

Section: Introductionmentioning

confidence: 99%

Distinct Transcriptional and Alternative Splicing Signatures of Decidual CD4+ T Cells in Early Human Pregnancy

Zeng

Liu

et al. 2017

Front. Immunol.

View full text Add to dashboard Cite

Decidual CD4+ T (dCD4 T) cells are crucial for the maternal-fetal immune tolerance required for a healthy pregnancy outcome. However, their molecular and functional characteristics are not well elucidated. In this study, we performed the first analysis of transcriptional and alternative splicing (AS) landscapes for paired decidual and peripheral blood CD4+ T (pCD4 T) cells in human early pregnancy using high throughput mRNA sequencing. Our data showed that dCD4 T cells are endowed with a unique transcriptional signature when compared to pCD4 T cells: dCD4 T cells upregulate 1,695 genes enriched in immune system process whereas downregulate 1,011 genes mainly related to mRNA catabolic process and the ribosome. Moreover, dCD4 T cells were observed to be at M phase, and show increased activation, proliferation, and cytokine production, as well as display an effector-memory phenotype and a heterogenous nature containing Th1, Th17, and Treg cell subsets. However, dCD4 T cells undergo a comparable number of upregulated and downregulated AS events, both of which are enriched in the genes related to cellular metabolic process. And the changes at the AS event level do not reflect measurable differences at the gene expression level in dCD4 T cells. Collectively, our findings provide a comprehensive portrait of the unique transcriptional signature and AS profile of CD4+ T cells in human decidua and help us gain more understanding of the functional characteristic of these cells during early pregnancy.

show abstract

“…Abnormal Tim-3 level might be associated with RSA (27). As described by Wang et al Tim-3 promotes T-helper balance (28).…”

Section: Introductionmentioning

confidence: 87%

A Review on Controversies about the Role of Immune and Inflammatory Systems in Implantation Process and Durability of Pregnancy

Ahmadi¹,

Shahsavar²,

Akbari³

2016

IJWHR

View full text Add to dashboard Cite

IntroductionAmong the controversies in reproduction science, role of immune and inflammatory systems in implantation process and durability of pregnancy is a hot topic nowadays. Some researchers and practitioners believe that administration of drugs such as prednisolone, aspirin or heparin can improve success rate of implantation and pregnancy through inhibiting coagulation, inflammatory and immune systems; while others believe that such systems not only do not have negative effect on rejecting blastocyst and embryo by itself but also are necessary for implantation and remodeling of uterine spiral arteries through secreting adhesive and angiogenic factors. Such controversies are proposed both in natural pregnancies resulting in spontaneous abortion as well as in successful and/or unsuccessful assisted reproductive technologies (ARTs). Recurrent spontaneous abortion (RSA) is defined as having 3 or more history of abortion (1). About the other issue, some researchers and practitioners are grumbling of low success rate of ARTs like in vitro fertilization (IVF). Infertility is a problem for 10%-15% of couples; most of which -but not all -require ART (2). The average fertilization rate of ART in previous researches has been reported about 30% (3) and this report is for 1998. It has been claimed in an article published in 2015 that this rate has improved in the recent decade (4). Even though at the first glance this rate seems low, but the interesting point is that in the claim of a valid reference (5) the chance of natural pregnancy for each intercourse per month does not go up more than 33%. Also this number has been reported in some studies up to 40% (6). Thus, we should not be grumbling of the low fertilization rate of ARTs. Finally we intend to represent and report our insights, reasoning and suggestions in the present review. MethodsThis systematic and critical review includes investigation of scientific data bases and tracing the citations and the references of the articles in order to find the root of the truth. Through this wisdom, we showed the mere that a content proposed in an indexed article is not a reason that this content is valid and able to be cited. Indeed, the researcher should regard and notice the reasoning, citations and protocol of his/her references during the literature review. This is the benefit point of systematic review rather than holistic and narrative reviews. Since some data were few, the time period of publications was not important to us. As the searching strategy, we used the Web of Science Core Collection and Google Scholar for finding articles other than ISI-WOS and the tracing mentioned in the above paragraph. Results and DiscussionRole of Immune System and Leukocytes In 2015, Ghafourian et al (1) by measuring the level of natural killer-cells (NKs) in blood of the RSA and the control group concluded that RSA patients in normal (non-preg- AbstractAmong the controversies about reproduction sciences, role of immune and inflammatory systems in implantation process and durability of...

show abstract

Programmed cell death-1 (PD-1) and T-cell immunoglobulin mucin-3 (Tim-3) regulate CD4⁺T cells to induce Type 2 helper T cell (Th2) bias at the maternal–fetal interface

Cited by 91 publications

References 32 publications

Estradiol Suppresses TLR4-triggered Apoptosis of Decidual Stromal Cells and Drives an Anti-inflammatory T_H2 Shift by Activating SGK1

Estradiol Suppresses TLR4-triggered Apoptosis of Decidual Stromal Cells and Drives an Anti-inflammatory T_H2 Shift by Activating SGK1

Distinct Transcriptional and Alternative Splicing Signatures of Decidual CD4+ T Cells in Early Human Pregnancy

A Review on Controversies about the Role of Immune and Inflammatory Systems in Implantation Process and Durability of Pregnancy

Contact Info

Product

Resources

About

Programmed cell death-1 (PD-1) and T-cell immunoglobulin mucin-3 (Tim-3) regulate CD4+T cells to induce Type 2 helper T cell (Th2) bias at the maternal–fetal interface

Cited by 91 publications

References 32 publications

Estradiol Suppresses TLR4-triggered Apoptosis of Decidual Stromal Cells and Drives an Anti-inflammatory TH2 Shift by Activating SGK1

Estradiol Suppresses TLR4-triggered Apoptosis of Decidual Stromal Cells and Drives an Anti-inflammatory TH2 Shift by Activating SGK1

Distinct Transcriptional and Alternative Splicing Signatures of Decidual CD4+ T Cells in Early Human Pregnancy

A Review on Controversies about the Role of Immune and Inflammatory Systems in Implantation Process and Durability of Pregnancy

Contact Info

Product

Resources

About

Programmed cell death-1 (PD-1) and T-cell immunoglobulin mucin-3 (Tim-3) regulate CD4⁺T cells to induce Type 2 helper T cell (Th2) bias at the maternal–fetal interface

Estradiol Suppresses TLR4-triggered Apoptosis of Decidual Stromal Cells and Drives an Anti-inflammatory T_H2 Shift by Activating SGK1

Estradiol Suppresses TLR4-triggered Apoptosis of Decidual Stromal Cells and Drives an Anti-inflammatory T_H2 Shift by Activating SGK1