Lgals9, also known as Galectin-9, is a member of the β -galactosidase family and plays a crucial role in immune regulation [4]. It is involved in multiple pathways, such as binding to cell-surface glycoprotein CD44 (LGALS9-CD44) in cell communication [1], and interacting with T cell inhibitory receptors like PD-1 and TIM-3 to regulate T cell death [3]. Lgals9 is important in various biological processes including those related to inflammation, cell adhesion, and immune cell function [1,3,5].

In a murine stroke model, extracellular vesicle-mediated Lgals9 delivery improved long-term functional recovery, and knockdown of Cd44, its receptor, partially reversed these therapeutic effects, inhibiting oligodendrocyte differentiation and remyelination, indicating Lgals9-CD44 signaling is critical after ischemic injury [1]. In preeclampsia mouse models, increased placental and plasma galectin-9 levels were observed. Galectin-9 administration induced preeclampsia-like phenotypes with increased CD11chigh dMφ and defective spiral arteries, while galectin-9 blockade or macrophage-specific CD44 deletion prevented such phenotypes [2].

In conclusion, Lgals9 is essential in immune regulation and cell-cell communication. Studies using gene-knockout (KO) or conditional-knockout (CKO) mouse models have revealed its significance in stroke and preeclampsia. These models help in understanding how Lgals9 functions in specific biological processes and disease conditions, providing potential treatment targets for these diseases.