Lgals9, also known as Galectin-9, is a member of the β-galactosidase family and plays a crucial role in immune regulation. It is involved in multiple pathways, such as binding to cell-surface glycoprotein CD44 and T cell immunoglobulin and mucin domain 3 (TIM-3), which are associated with immune cell apoptosis, activation, and immune-related disease processes [2,3,4].

In a murine stroke model, extracellular vesicle-mediated Lgals9 delivery improved long-term functional recovery, and knockdown of Cd44 reversed these therapeutic effects, inhibiting oligodendrocyte differentiation and remyelination, suggesting Lgals9-CD44 as a critical signaling pathway after ischemic injury [1]. In preeclampsia, galectin-9 from trophoblasts activates CD11chigh decidual macrophages via CD44 binding, suppressing uterine spiral artery remodeling. Galectin-9 blockade or macrophage-specific CD44 deletion prevents preeclampsia-like phenotypes in mouse models [3].

In conclusion, Lgals9 is essential in immune regulation and has a significant impact on diseases like stroke and preeclampsia. The use of gene-knockout or conditional-knockout mouse models in these studies has revealed its role in specific biological processes, providing valuable insights into potential treatment strategies for these diseases.

References:

1. Han, Bing, Zhou, Shunheng, Zhang, Yuan, Jiang, Wei, Yao, Honghong. 2024. Integrating spatial and single-cell transcriptomics to characterize the molecular and cellular architecture of the ischemic mouse brain. In Science translational medicine, 16, eadg1323. doi:10.1126/scitranslmed.adg1323. https://pubmed.ncbi.nlm.nih.gov/38324639/

2. Zhao, Lizhen, Cheng, Shaoyun, Fan, Lin, Zhang, Bei, Xu, Shengwei. 2021. TIM-3: An update on immunotherapy. In International immunopharmacology, 99, 107933. doi:10.1016/j.intimp.2021.107933. https://pubmed.ncbi.nlm.nih.gov/34224993/

3. Li, Yanhong, Sang, Yifei, Chang, Yunjian, Wu, Ligang, Du, Meirong. 2024. A Galectin-9-Driven CD11chigh Decidual Macrophage Subset Suppresses Uterine Vascular Remodeling in Preeclampsia. In Circulation, 149, 1670-1688. doi:10.1161/CIRCULATIONAHA.123.064391. https://pubmed.ncbi.nlm.nih.gov/38314577/

4. Yang, Riyao, Sun, Linlin, Li, Ching-Fei, Yu, Dihua, Hung, Mien-Chie. 2021. Galectin-9 interacts with PD-1 and TIM-3 to regulate T cell death and is a target for cancer immunotherapy. In Nature communications, 12, 832. doi:10.1038/s41467-021-21099-2. https://pubmed.ncbi.nlm.nih.gov/33547304/