About: TIGIT is a research topic. Over the lifetime, 813 publications have been published within this topic receiving 24120 citations. The topic is also known as: V-set and transmembrane domain-containing protein 3 & VSIG9, VSTM3.
TL;DR: It is shown that TIGIT is expressed by all human NK cells, that it binds PVR and PVRL2 but not PVRL3 and that it inhibits NK cytotoxicity directly through its ITIM, providing an “alternative self” mechanism for MHC class I inhibition.
Abstract: NK cell cytotoxicity is controlled by numerous NK inhibitory and activating receptors. Most of the inhibitory receptors bind MHC class I proteins and are expressed in a variegated fashion. It was recently shown that TIGIT, a new protein expressed by T and NK cells binds to PVR and PVR-like receptors and inhibits T cell activity indirectly through the manipulation of DC activity. Here, we show that TIGIT is expressed by all human NK cells, that it binds PVR and PVRL2 but not PVRL3 and that it inhibits NK cytotoxicity directly through its ITIM. Finally, we show that TIGIT counter inhibits the NK-mediated killing of tumor cells and protects normal cells from NK-mediated cytoxicity thus providing an “alternative self” mechanism for MHC class I inhibition.
TL;DR: Co-inhibitory receptors, such as CTLA-4 and PD-1, have an important role in regulating T cell responses and have proven to be effective targets in the setting of chronic diseases where constitutive co- inhibitory receptor expression on T cells dampens effector T-cell responses.
TL;DR: The data suggest that TIGIT exerts immunosuppressive effects by binding to poliovirus receptor and modulating cytokine production by dendritic cells.
Abstract: Here we have identified a surface protein, TIGIT, containing an immunoglobulin variable domain, a transmembrane domain and an immunoreceptor tyrosine-based inhibitory motif that was expressed on regulatory, memory and activated T cells. Poliovirus receptor, which is expressed on dendritic cells, bound TIGIT with high affinity. A TIGIT-Fc fusion protein inhibited T cell activation in vitro, and this was dependent on the presence of dendritic cells. The binding of poliovirus receptor to TIGIT on human dendritic cells enhanced the production of interleukin 10 and diminished the production of interleukin 12p40. Knockdown of TIGIT with small interfering RNA in human memory T cells did not affect T cell responses. TIGIT-Fc inhibited delayed-type hypersensitivity reactions in wild-type but not interleukin 10-deficient mice. Our data suggest that TIGIT exerts immunosuppressive effects by binding to poliovirus receptor and modulating cytokine production by dendritic cells.
TL;DR: This work has shown that natural killer cell killing of various tumors is inhibited in the presence of various F. nucleatum strains, and identified a bacterium-dependent, tumor-immune evasion mechanism in which tumors exploit the Fap2 protein of F. nucleus to inhibit immune cell activity via TIGIT.
TL;DR: A key role is defined for TIGIT in inhibiting chronic CD8(+) T cell-dependent responses to tumor formation and chronic immune responses to chronic viral infection.