Problem: To understand the mechanisms of action of Tim-3 at the maternal-fetal interface and explore how Tim-3 might be involved in the pathogenesis of abortion by constructing an in vitro trophoblast-lymphocyte system.

Methods Of Study: Female CBA/J × male DBA/2 matings were used as the abortion-prone model and CBA/J × male BALB/c matings as control. The expression of Tim-3 at the maternal-fetal interface and in the peripheral blood lymphocytes was measured by immunohistochemistry and Western blotting. The proliferation index of lymphocytes and levels of Th1/Th2-derived cytokines in peripheral blood and in the co-culture system were determined using CCK-8 assay and ELISA, respectively.

Results: The expression level of Tim-3 was higher in abortion-prone matings than that of control (P < .05). A preponderance of Th1 was observed in the co-culture system in the abortion-prone mating group. Recombinant Tim-3 Ig reversed the imbalance of Th1/Th2 immunity of abortion-prone matings by suppressing the secretion of IFN-γ and IL-2 but had no direct effect on the generation of IL-4.

Conclusion: Tim-3 might contribute to successful pregnancy by restraining Th1 bias, and the maternal immune system might develop a strategy including upregulation of Tim-3 at the maternal-fetal interface and in peripheral blood so as to maintain moderate inflammatory responses against miscarriage.

Download full-text PDF

Source
http://dx.doi.org/10.1111/aji.12775DOI Listing

Publication Analysis

Top Keywords

tim-3 maternal-fetal
8
maternal-fetal interface
8
matings control
8
peripheral blood
8
upregulation tim-3
4
tim-3 expression
4
expression feto-maternal
4
feto-maternal interface
4
interface explain
4
explain embryo
4

Similar Publications

Involvement of Tim-3 in Maternal-fetal Tolerance: A Review of Current Understanding.

Int J Biol Sci

January 2025

Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai 200011, China.

As the first T cell immunoglobulin mucin (Tim) family member to be identified, Tim-3 is a powerful immune checkpoint that functions in immunoregulation and induction of tolerance. Conventionally, Tim-3 is considered to play a role in adaptive immunity, especially in helper T cell-mediated immune responses. As researches progress, Tim-3 has been detected in a wider range of cell types, modulating cell function through ligand-receptor interactions and other pathways.

View Article and Find Full Text PDF
Article Synopsis
  • Toxoplasma gondii infection negatively impacts pregnancy by disrupting the production of Galectin-9 (Gal-9) in decidual macrophages, which is essential for maintaining maternal-fetal tolerance.
  • The infection triggers an increase in phosphorylated JNK and FOXO1 levels, resulting in decreased Gal-9 expression due to FOXO1 binding more tightly to the Gal-9 gene promoter.
  • The loss of Gal-9 leads to increased activation of decidual natural killer cells, which is linked to worse pregnancy outcomes in mice infected with T. gondii.
View Article and Find Full Text PDF
Article Synopsis
  • Extravillous trophoblasts (EVTs) invade the uterus early in pregnancy, remodeling spiral arteries into larger blood vessels, with ongoing debate about the role of immune and stromal cells in this process as pregnancy progresses.
  • A multiomics study was conducted to analyze around 500,000 cells and numerous arteries from pregnant individuals, revealing significant changes in maternal immune cell populations as gestational age increases.
  • The study developed a model of spiral artery remodeling (SAR) that details how EVT invasion is linked to the regulation of blood vessel growth and immune cell interaction, promoting a safe maternal-fetal environment.
View Article and Find Full Text PDF

Myeloid-derived suppressor cells (MDSCs) play a key role in maintaining maternal-fetal tolerance for a successful pregnancy, but the role of MDSCs in abnormal pregnancy caused by Toxoplasma gondii infection is unknown. Herein, we revealed a distinct mechanism by which T-cell immunoglobulin domain and mucin domain containing protein-3 (Tim-3), an immune checkpoint receptor that balances maternal-fetal tolerance during pregnancy, contributes to the immunosuppressive function of MDSCs during T. gondii infection.

View Article and Find Full Text PDF

Immune checkpoint inhibitors and reproductive failures.

J Reprod Immunol

March 2023

Reproduction Medical Center, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, PR China. Electronic address:

The human conceptus is a semi-allograft, which is antigenically foreign to the mother. Hence, the implantation process needs mechanisms to prevent allograft rejection during successful pregnancy. Immune checkpoints are a group of inhibitory pathways expressed on the surface of various immune cells in the form of ligand receptors.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!