TIGIT Stimulation Suppresses Autoimmune Uveitis by Inhibiting Th17 Cell Infiltration.

ABSTRACT

T cell immunoglobulin and ITIM domain (TIGIT) is an immune checkpoint molecule that suppresses T cell activation and promotes an immunosuppressive environment to suppress autoimmune diseases. However, the impact of a TIGIT agonist as a treatment for ocular autoimmune disease has not been investigated. We examined TIGIT expression on Th17 and Treg cells, the role of TIGIT on experimental autoimmune uveitis (EAU) and Th17 cells, and the impact of Treg generation following TIGIT stimulation. TIGIT stimulation at the onset of clinical symptoms reduced the severity of uveitis and suppressed infiltration of Th17 cells into the eye. Further, Tregs from mice treated with the TIGIT agonist were capable of suppressing EAU in recipient mice. This report demonstrates that stimulation of TIGIT at onset of disease suppresses symptoms and allows for induction of regulatory immunity that provides resistance to uveitis.