Regulation of T cell trafficking by the T cell immunoglobulin and mucin domain 1 glycoprotein

• T cell immunoglobulin and mucin domain 1 (TIM-1) controls T helper (Th) cells Th1 and Th17 during inflammation and autoimmunity.
• TIM-1 binds to all three selectins in vitro and is a major P-selectin ligand in vivo.
• TIM-1 IgV domain-selectin binding is a unique feature in leukocyte trafficking.
• P-selecting glycoprotein ligand-1 (PSGL-1) and TIM-1 represent a new form of concurrency in leukocyte trafficking.

Leukocyte trafficking is generally considered the initial stage of any immune response, and it involves a multistep intravascular process including capture, rolling, activation, arrest, crawling, and transmigration. Both capture and rolling are predominantly mediated by selectins, which allow circulating leukocytes to sense activating signals on the endothelium and adhere to vessel walls. In this review, we discuss recent data showing that the T cell immunoglobulin and mucin domain 1 (TIM-1) protein is a major ligand for endothelial P-selectin, mediating T helper (Th) cell Th1 and Th17 trafficking in inflamed tissues. We highlight structural and functional features showing that TIM-1 can be included in the restricted group of major adhesion receptors involved in leukocyte trafficking with a pathophysiological role in inflammation and autoimmunity.