Expression of co-signaling molecules TIM-3/Galectin-9 at the maternal-fetal interface
Year: 2025
Type: article
Abstract: During early pregnancy, fetal placental tissue implants into maternal decidual tissue, forming a unique interface where maternal immune cells do not reject the invading fetal cells. Given the roles of Galectin-9 and Tim-3 in tumor immune regulation, studying their distribution and function at this interface may provide insights into recurrent pregnancy loss. This study uses single-cell transcriptomics, spatial transcriptomics, and multiplex immunohistochemistry to examine the expression and localization of Galectin-9 and TIM-3. Hormone-induced decidualization of immortalized human endometrial stromal cells was conducted to investigate Galectin-9 expression. The major immune cells in the maternal decidua, such as T cells, NK cells, and macrophages, co-express Galectin-9 and TIM-3. Unlike TIM-3, Galectin-9 is also highly expressed in endothelial cells and decidualized stromal cells. Among placenta-derived cells, Hofbauer cells (HB) and Placenta-associated maternal monocytes/macrophages (PAMM) exhibit high expression of both Galectin-9 and TIM-3, while trophoblast cells show relatively low levels of expression. Additionally, hormone-induced decidualization significantly upregulates Galectin-9 expression in endometrial stromal cells. The research results suggest that Galectin-9 and TIM-3, as important immune co-signaling molecules, may play a crucial role in maintaining the immune-tolerant microenvironment at the maternal-fetal interface. Additionally, the association between decidualization and Galectin-9 expression reveals its potential role in pregnancy maintenance, providing new insights for the study of adverse pregnancy outcomes. • TIM-3/Galectin-9 Expression and Localization at the Maternal-Fetal Interface • Utilizing advanced techniques, including single-cell transcriptomics, spatial transcriptomics, and multiplex immunohistochemistry, we elucidated the co-expression of TIM-3 and Galectin-9 in decidual immune cells at the maternal-fetal interface, unveiling their novel roles in immune tolerance. • Correlation Between Decidualization and Galectin-9 Expression • Our research revealed a strong association between Galectin-9 expression and the process of decidualization, with a marked increase in Galectin-9 levels in decidual stromal cells as decidualization progresses. • Novel Insights into Immune Regulation at the Maternal-Fetal Interface • Contrary to previous assumptions, our findings identified Hofbauer cells as the primary fetal source of Galectin-9, rather than trophoblasts, offering a fresh perspective on the mechanisms underlying immune tolerance at the maternal-fetal interface.
Source: Placenta
Authors: Jingliang Xu, Xuqing He, Sujuan Zhang, Li Li, Penghao Li
Institutions: Shantou University, Shantou University Medical College
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,720
OpenAlex ID: W4408220703