Impaired Gal-9 Dysregulates the PBMC-Induced Th1/Th2 Imbalance in Abortion-Prone Matings

Abstract

Recurrent miscarriage is defined as the loss of 3 or more consecutive pregnancies; however, the underlying immunologic mechanisms that trigger pregnancy loss remain largely unelucidated. Galectin-9 (Gal-9) may modulate a variety of biologic functions and play an important role in Th1/Th2 immune deviation. To analyze the mechanism of Gal-9 in abortion, we used the classical abortion-prone mouse model (DBA/2-mated CBA/J mice) to detect the expression of Gal-9 at the maternal-fetal interface. We also mimicked the immune environment of pregnancy by culturing trophoblast cells with peripheral blood mononuclear cells (PBMCs) to explore how Gal-9 might be involved in the pathogenesis of abortion. We found that the expression levels of Gal-9 in abortion-prone matings were lower than that for controls. Using a coculture system, we detected a Th1 preponderance in the coculture from abortion-prone matings. Furthermore, Gal-9 blockade augmented the imbalance of Th1/Th2 immunity in abortion-prone matings by promoting the secretion of Th1-derived cytokines in coculture, while there was a Th2 preponderance when we administered recombinant Gal-9. In conclusion, our results suggest that the Gal-9 signal is important for the regulation of PBMC function toward a Th2 bias at the maternal-fetal interface, which is beneficial for the maintenance of a normal pregnancy.

Immunosuppressive Property of MSCs Mediated by Cell Surface Receptors

“…These regulatory effects on T cells may be related to the expression of Gal-9 expressed on MSCs (5,63,67). Further animal studies showed similar results from in-vitro studies before, under the PBMC co-coculture with recombinant Gal-9, Th1 cells were inhibited while Th2-derived cytokines are predominant (66,70,71). We speculate that different expression levels of TIM-3 expressed in Th1 and Th2 cells may lead to the opposite outcome.…”

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

“…Activated T cells express galectin-1, which induces down-stream apoptosis ( 159 ), repressing Th1 immunity. Galectin-9 (Gal-9), which belongs to the β-galactoside-binding lectin family, participates in the regulation of Th1/Th2 balance via suppressing the production of Th1 cytokine, TNF-α, and promoting the secretion of Th2 type cytokine, IL-4 ( 160 ). Lastly, during pregnancy, major immunomodulatory molecules from the trophoblast, for example, HLA-G5 ( 161 ), favor a shift to Th2 immunity, which may participate in the upkeep of maternal tolerance to fetal antigens ( 77 ).…”

Danggui-Yimucao Herb Pair Can Protect Mice From the Immune Imbalance Caused by Medical Abortion and Stabilize the Level of Serum Metabolites

“…Studies showed that Th1/Th2 was involved in both the maintenance of pregnancy and abortion ( Saito et al, 2010 ; He et al, 2018a ). The transcription factor T-bet drove Th1 differentiation, while transcription factor GATA-3 drove Th2 differentiation ( Kim et al, 2014 ).…”