scholarly journals Decidual NR2F2-Expressing CD4+ T Cells Promote TH2 Transcriptional Program During Early Pregnancy

2021 ◽  
Vol 12 ◽  
Author(s):  
Yikong Lin ◽  
Di Zhang ◽  
Yangyang Li ◽  
Yunyun Li ◽  
Bin Li ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Fate ◽  
Immune Tolerance ◽  
Early Pregnancy ◽  
Normal Pregnancy ◽  
Cell Fate Specification ◽  
Prediction And Prevention ◽  
Potential Biomarker ◽  
Unexplained Recurrent Spontaneous Abortion ◽  
Th2 Differentiation

A unique immunotolerant microenvironment with Th2 bias in the decidua provides an essential security for successful pregnancy. The disorganized maternal-fetal immune tolerance contributes to more than 50% of unexplained recurrent spontaneous abortion (RSA). How the Th2 bias is developed at the maternal-fetal interface remains undefined. NR2F2, a member of steroid/thyroid nuclear receptor superfamily, is endowed with diverse importance in cell-fate specification, organogenesis, angiogenesis, and metabolism. Here, we showed that NR2F2 was absolutely highly expressed in decidual CD4+T(dCD4+T) cells, but not in peripheral circulating CD4+T cells during early pregnancy. Decidual NR2F2-expressing CD4+T cells dominantly produced Th2 cytokines. In unexplained RSA patients, NR2F2 expression in dCD4+T cells was significantly decreased, accompanied with disordered phenotype of dCD4+T cells. Furthermore, overexpression of NR2F2 promoted the Th2 differentiation of naive CD4+T cells. Immunoprecipitation experiment confirmed the binding relationship between GATA-3 and NR2F2, which implied GATA-3 may be an important interactive element involved in the immunoregulatory process of NR2F2. This study is the first to reveal a previously unappreciated role for NR2F2-mediated dCD4+T cells in maternal-fetal immune tolerance and maintenance of normal pregnancy, in the hope of providing a potential biomarker for prediction and prevention of clinical unexplained RSA.

scholarly journals Early Pregnancy Human Decidua Gamma/Delta T Cells Exhibit the Tissue Resident and Specific Functional characteristics

2021 ◽  
Author(s):  
Shuo Yang ◽  
Ting Feng ◽  
Yong Cheng Ma ◽  
Hao Tie Wang ◽  
Qin Hong Chen ◽  
...  
Keyword(s):  
T Cells ◽  
Growth Factors ◽  
Fetal Growth ◽  
Early Pregnancy ◽  
Mononuclear Cells ◽  
A549 Cells ◽  
Γδ T Cells ◽  
Normal Pregnancy ◽  
Peripheral Blood Mononuclear ◽  
Research Attention

Abstract Background: A successful pregnancy is a complicated process that builds upon two aspects of the maternal immune system that needs to be balanced. As one of the dominant groups of cells at the maternal fetal interface, the decidual γδ T cells have attracted great research attention in normal pregnancy or miscarriage. However, the role of γδ T cells in fetal growth still remains poorly studied. Results: In this study, we identified γδ T cells were enriched and resident in decidua during early pregnancy, and early decidual γδ T cells were involved in the secretion of growth factors, including growth differentiation factor 15 (GDF15) and bone morphogenetic protein 1 (BMP1). Decrease of these growth factors could impaire fetal development, resulting in fetal growth restriction. We also observed that the early decidual γδ T cells exhibited stronger cytokine secretion characteristic, but its cytotoxicity against A549 cells was weaker, when compared with the γδ T cells in peripheral blood mononuclear cells (PBMCs). In addition, the functional abilities of early decidual γδ T cells in promoting trophoblast cell proliferation, migration, invasion and tube formation were also significantly stronger than those in γδ T cells of PBMCs. Conclusions: These findings highlighted the importance of γδ T cells in fetal growth and maternal immune tolerance during pregnancy, which is different from γδ T cells in PBMCs, and encouraged further research in this field.

Bioinformatics Analysis Identifies CPZ as a Tumor Immunology Biomarker For Gastric Cancer

2020 ◽  
Vol 15 ◽  
Author(s):  
Yuan Gu ◽  
Ying Gao ◽  
Xiaodan Tang ◽  
Huizhong Xia ◽  
Kunhe Shi
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
Signaling Pathway ◽  
Tumor Immunology ◽  
Bioinformatics Analysis ◽  
Human Cancer ◽  
Disease Free Survival ◽  
Kaplan Meier ◽  
Potential Biomarker ◽  
Pathway Regulation

Background: Gastric cancer (GC) is one of the most common malignancies worldwide. However, the biomarkers for the prognosis and diagnosis of Gastric cancer were still need. Objective: The present study aimed to evaluate whether CPZ could be a potential biomarker for GC. Method: Kaplan-Meier plotter (http://kmplot.com/analysis/) was used to determine the correlation between CPZ expression and overall survival (OS) and disease-free survival (DFS) time in GC [9]. We analyzed CPZ expression in different types of cancer and the correlation of CPZ expression with the abundance of immune infiltrates, including B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells, via gene modules using TIMER Database. Results: The present study identified that CPZ was overexpressed in multiple types of human cancer, including Gastric cancer. We found that overexpression of CPZ correlates to the poor prognosis of patients with STAD. Furthermore, our analyses show that immune infiltration levels and diverse immune marker sets are correlated with levels of CPZ expression in STAD. Bioinformatics analysis revealed that CPZ was involved in regulating multiple pathways, including PI3K-Akt signaling pathway, cGMP-PKG signaling pathway, Rap1 signaling pathway, TGF-beta signaling pathway, regulation of cell adhesion, extracellular matrix organization, collagen fibril organization, collagen catabolic process. Conclusion: This study for the first time provides useful information to understand the potential roles of CPZ in tumor immunology and validate it to be a potential biomarker for GC.

scholarly journals SFTPA1 is a potential prognostic biomarker correlated with immune cell infiltration and response to immunotherapy in lung adenocarcinoma

2021 ◽  
Author(s):  
Lu Yuan ◽  
Xixi Wu ◽  
Longshan Zhang ◽  
Mi Yang ◽  
Xiaoqing Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Lung Adenocarcinoma ◽  
Expression Profile ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Regulatory Pathways ◽  
Chronic Lung Diseases ◽  
Potential Biomarker

AbstractPulmonary surfactant protein A1 (SFTPA1) is a member of the C-type lectin subfamily that plays a critical role in maintaining lung tissue homeostasis and the innate immune response. SFTPA1 disruption can cause several acute or chronic lung diseases, including lung cancer. However, little research has been performed to associate SFTPA1 with immune cell infiltration and the response to immunotherapy in lung cancer. The findings of our study describe the SFTPA1 expression profile in multiple databases and was validated in BALB/c mice, human tumor tissues, and paired normal tissues using an immunohistochemistry assay. High SFTPA1 mRNA expression was associated with a favorable prognosis through a survival analysis in lung adenocarcinoma (LUAD) samples from TCGA. Further GeneOntology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses showed that SFTPA1 was involved in the toll-like receptor signaling pathway. An immune infiltration analysis clarified that high SFTPA1 expression was associated with an increased number of M1 macrophages, CD8+ T cells, memory activated CD4+ T cells, regulatory T cells, as well as a reduced number of M2 macrophages. Our clinical data suggest that SFTPA1 may serve as a biomarker for predicting a favorable response to immunotherapy for patients with LUAD. Collectively, our study extends the expression profile and potential regulatory pathways of SFTPA1 and may provide a potential biomarker for establishing novel preventive and therapeutic strategies for lung adenocarcinoma.

scholarly journals Maternal Neutrophil Depletion Fails to Avert Systemic Lipopolysaccharide-Induced Early Pregnancy Defects in Mice

2021 ◽  
Vol 22 (15) ◽  
pp. 7932
Author(s):  
Sourav Panja ◽  
John T. Benjamin ◽  
Bibhash C. Paria
Keyword(s):  
Early Pregnancy ◽  
Normal Pregnancy ◽  
Mrna Levels ◽  
Interesting Approach ◽  
Blastocyst Implantation ◽  
Neutrophil Depletion ◽  
Underlying Mechanisms ◽  
Myd88 Signaling ◽  
Induced Defects ◽  
Dose Dependent

Maternal infection-induced early pregnancy complications arise from perturbation of the immune environment at the uterine early blastocyst implantation site (EBIS), yet the underlying mechanisms remain unclear. Here, we demonstrated in a mouse model that the progression of normal pregnancy from days 4 to 6 induced steady migration of leukocytes away from the uterine decidual stromal zone (DSZ) that surrounds the implanted blastocyst. Uterine macrophages were found to be CD206+ M2-polarized. While monocytes were nearly absent in the DSZ, DSZ cells were found to express monocyte marker protein Ly6C. Systemic endotoxic lipopolysaccharide (LPS) exposure on day 5 of pregnancy led to: (1) rapid (at 2 h) induction of neutrophil chemoattractants that promoted huge neutrophil infiltrations at the EBISs by 24 h; (2) rapid (at 2 h) elevation of mRNA levels of MyD88, but not Trif, modulated cytokines at the EBISs; and (3) dose-dependent EBIS defects by day 7 of pregnancy. Yet, elimination of maternal neutrophils using anti-Ly6G antibody prior to LPS exposure failed to avert LPS-induced EBIS defects allowing us to suggest that activation of Tlr4-MyD88 dependent inflammatory pathway is involved in LPS-induced defects at EBISs. Thus, blocking the activation of the Tlr4-MyD88 signaling pathway may be an interesting approach to prevent infection-induced pathology at EBISs.

Sign in / Sign up

Export Citation Format

Share Document