Role of the KLRG1 pathway in the immune response

Abstract Killer cell lectin-like receptor G1 (KLRG1) is a C-type lectin inhibitory receptor that contains an immunoreceptor tyrosine-based inhibitory motif (ITIM) in its cytoplasmic domain. KLRG1 is well conserved in mammals and is mostly expressed on subsets of T cells and natural killer (NK) cells. Upon binding to its ligands, N-cadherin and E-cadherin, the phosphatases SHP-2 and SHIP-1 are recruited to the cytoplasmic tail of KLRG1. Some studies have proposed that KLRG1 is a marker of senescence, while other studies suggest that KLRG1 is a marker of recently activated cells. In addition, although KLRG1 inhibitory potential has been established in vitro, it is unclear whether KLRG1 inhibits NK cells and CD8+ T cells in vivo. To address its exact role, we have used CRISPR technology to generate mice deficient for KLRG1 and mice conditionally deficient for KLRG1 in the NK cell lineage. We found that NK cell frequency and number is not effected and that NK cell development is globally intact in KLRG1 deficient mice. The role of KLRG1 during viral infections and tumor development is currently being investigated.