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Liver and lymph node sinusoidal endothelial cell C-type lectin (LSECtin), encoded by the CLEC4G gene, is a type II transmembrane protein belonging to the C-type lectin receptor (CLR) family. It is predominantly expressed on the sinusoidal endothelial cells of the liver and lymph nodes, as well as on certain subsets of macrophages and dendritic cells (UniProt: Q6UXB4). LSECtin functions as a calcium-dependent carbohydrate-recognition receptor, specifically binding to N-glycans containing terminal GlcNAc or mannose residues (PubMed: 14688331). In the context of immunology, LSECtin acts as a potent negative regulator of T-cell responses; by binding to CD44 on T cells, it inhibits their proliferation and the production of inflammatory cytokines like IFN-gamma (PubMed: 19172134). This inhibitory role is often exploited in the tumor microenvironment to facilitate immune evasion, particularly in hepatic and colorectal cancers (PubMed: 21242515). Furthermore, LSECtin has been identified as a co-receptor for several viruses, including Ebola, SARS-CoV, and SARS-CoV-2, where it facilitates viral attachment and entry (PubMed: 32405061). Therapeutic development is currently focused on monoclonal antibodies that block the LSECtin-CD44 axis to restore anti-tumor immunity and glycomimetic compounds designed to prevent viral infection.
Blockade of the LSECtin-CD44 interaction to enhance T-cell mediated immunity; competitive inhibition of viral binding to the carbohydrate recognition domain.
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