TIM3/HAVCR2/CD366 [MD163]

TIMs are type I transmembrane glycoproteins with one Ig-like V-type domain and a Ser/Thr-rich mucin stalk. TIM-3 is expressed on the surface of effector T cells (CD4+Th1 and CD8+Tc1) but not on helper T cells (CD4+Th2 and CD8+Tc2). In chronic inflammation, autoimmune disorders, and some cancers, TIM-3 is upregulated on several other hematopoietic cell types. The Ig domain of TIM-3 interacts with a ligand on resting but not activated Th1 and Th2 cells. The glycosylated Ig domain of TIM-3 binds cell-associated galectin-9. This induces TIM-3 Tyr phosphorylation and pro-apoptotic signaling. TIM-3 functions as a negative regulator of Th1 cell activity. Its blockade results in increased IFN-gamma production, Th1 cell proliferation and cytotoxicity, regulatory T cell development, and increases in macrophage and neutrophil infiltration into sites of inflammation.