TIM-3 and Galectin-9 Signaling Pahtway

1. TIM-3 and Galectin-9 Signaling Pahtway T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), otherwise known as Hepatitis A virus cellular receptor 2 (HAVCR2), is a protein that in humans is encoded by the HAVCR2 gene. TIM-3 belongs to TIM family cell surface receptor proteins. These proteins share a similar structure, in which the extracellular region consists of membrane distal single variable immunoglobulin domain (IgV) and a glycosylated mucin domain of variable length located closer to the membrane. Intracellular domain of TIM-3 is called C-terminal cytoplasmic tail. It contains five conserved tyrosine residues that interact with multiple components of T-cell receptor (TCR) complex and negatively regulate its function. TIM-3 was first described in 2002, and then the researchers found that it expressed on IFNγ producing CD4+ Th1 and CD8+ Tc1 cells. Later, the expression was found in Th17 cells, regulatory cells(Tregs), and innate immune cells (dendritic cells, NK cells, monocytes). Galectin-9 is one of the most studied ligand for TIM-3(HAVCR2). In human, it is encoded by the LGALS9 gene. And it has N- and C- terminal carbohydrate-binding domains connected by a link peptide. Multiple alternatively spliced transcript variants have been found for this gene. From the existing research, we can see that Galectin-9 can interact with CLEC7A, CD137, CD40 and regulate different function which independent TIM-3. For example, interaction with CD40 on T-cells induces their proliferation inhibition and cell death. https://www.creative-diagnostics.com/tim-3-galectin-9-signaling-pathway.htm