KLRG1

KLRG1 is an acronym for "killercell lectin-like receptor1". KGLR1 belongs to the killer cell lectin-like receptor (KLR) family. This is a group of transmembrane proteins that are preferentially expressed in NK cells (Martin MD et al. 2018). The coding gene is located on chromosome 12p13.31.

KLRG1 is a lymphocyte co-inhibitory or immune checkpoint receptor expressed predominantly on late differentiated effector and effector memory CD8 + T and NK cells. Its ligands are E-cadherin and N-cadherin (Ito M et al. (2006) with similar affinities. KLRG1 is also considered a "senescent" marker (see immune senescence below) and, together with other co-inhibitory receptors, a "depletion" marker of NK cells (Melis L et al (2014).

In viral infections, antigen-specific CD8+ T cells targeting persistent viruses (e.g. human immunodeficiency virus and Epstein-Barr virus) have been shown to have low CD127 and high KLRG1 expressions, whereas CD8+ T cells targeting resolved viral antigens (e.g. FLU) typically have high CD127 and low KLRG1 expressions (Bengsch B et al. 2007).

NK cells expressing the surface marker KLRG1 in the blood and liver are able to kill activated stellate cells in the liver. These in turn contribute to liver fibrosis and subsequent liver dysfunction. There may be therapeutic opportunities here to limit fibrosis of the liver (Wijaya RS et al 2019).

Primary biliary cholangitis (PBC) also involves invasion of cytotoxic KLRG1+ lymphocytes in the portal area of the PBC liver. In PBC, hepatic KLRG1 gene expression and KLRG1+ lymphocyte abundance are positively correlated with disease biomarkers used as measures of clinical trial outcome (Li Y et al. 2019).

1. Bengsch B et al. (2007) Analysis of CD127 and KLRG1 expression on hepatitis C virus-specific CD8+ T cells reveals the existence of different memory T-cell subsets in the peripheral blood and liver. J Virol 81:945-53.
2. Ito M et al (2006) Killer cell lectin-like receptor G1 binds three members of the classical cadherin family to inhibit NK cell cytotoxicity. J Exp Med. 203:289-295.
3. Li Y et al (2019) Cytotoxic KLRG1 expressing lymphocytes invade portal tracts in primary biliary cholangitis. J Autoimmune 103:102293
4. Martin MD et al (2018) Defining memory CD8 T cell. Front. Immunol, 20 Nov 2018
5. Melis L et al (2014) Senescence marker killer cell lectin-like receptor G1 (KLRG1) contributes to TNF-α production by interaction with its soluble E-cadherin ligand in chronically inflamed joints. Annals of the Rheumatic Diseases 73: 1223-31
6. Wijaya RS et al (2019) KLRG1+ natural killer cells exert a novel antifibrotic function in chronic hepatitis B. J Hepatol 71:252-264.