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.
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http://dx.doi.org/10.1111/aji.12775 | DOI Listing |
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 PDFParasit Vectors
July 2024
Department of Immunology, Binzhou Medical University, Yantai, 264003, Shandong, People's Republic of China.
Nature
July 2023
Department of Pathology, Stanford University, Stanford, CA, USA.
PLoS Pathog
April 2023
Department of Immunology, Binzhou Medical University, Yantai, Shandong, P. R. China.
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 PDFJ 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.
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