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), and is associated with processes like T cell apoptosis, cell communication, and immune cell regulation [2,3,4,5].

In a murine stroke model, extracellular vesicle-mediated Lgals9 delivery improved long-term functional recovery, and knockdown of Cd44 reversed these effects, inhibiting oligodendrocyte differentiation and remyelination, indicating its role in stroke recovery [1]. In preeclampsia, trophoblast-derived galectin-9 activates a CD11chigh subpopulation of decidual macrophages via CD44 binding, suppressing spiral artery remodeling. Galectin-9 blockade or macrophage-specific CD44 deletion in mouse models prevented preeclampsia-like phenotypes [3].

In conclusion, Lgals9 is essential in immune regulation and has significant implications in diseases such as stroke and preeclampsia. Studies using gene knockdown or conditional knockout (CKO) in mouse models have revealed its role in promoting recovery after stroke and in the pathogenesis of preeclampsia, providing potential therapeutic targets 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/

5. Li, Qi, Wang, Guochong, Yuan, Zihang, Zhang, Zhonghui, Liu, Chen. 2024. Circulating CD8 + LGALS9 + T Cell Population Exhibiting Low Cytotoxic Characteristics are Decreased in Patients with Systemic Lupus Erythematosus. In Immunologic research, 72, 1238-1246. doi:10.1007/s12026-024-09522-4. https://pubmed.ncbi.nlm.nih.gov/39046608/