C-type lectin domain family 4 member C (CLEC4C) (CLEC4C)

C-type lectin domain family 4 member C (CLEC4C), also known as CD303 or BDCA-2, is a type II transmembrane glycoprotein exclusively expressed on human plasmacytoid dendritic cells (pDCs) (UniProt: Q8WTT0). It belongs to the C-type lectin superfamily and functions as a receptor involved in antigen capture and the regulation of immune responses (NCBI Gene: 170482). Ligation of CLEC4C by specific antibodies or ligands triggers a signaling cascade that potently inhibits the production of type I interferons (IFN-I) and other pro-inflammatory cytokines by pDCs (PubMed: 36069818). Because the chronic overproduction of IFN-I is a central driver in the pathogenesis of autoimmune diseases like systemic lupus erythematosus (SLE), CLEC4C has emerged as a significant therapeutic target. The monoclonal antibody litifilimab (BIIB059) targets CLEC4C to reduce the pathogenic IFN-I signature and has shown efficacy in clinical trials for both systemic and cutaneous lupus (PubMed: 32726550). This target allows for the modulation of pDC activity without the need for broad cellular depletion, potentially offering a more refined therapeutic approach for interferon-mediated diseases.

Other names

CD303Blood dendritic cell antigen 2BDCA-2CLECSF7DLEC

Litifilimab is a humanized IgG1 monoclonal antibody that binds to CLEC4C on the surface of plasmacytoid dendritic cells. This binding leads to the rapid internalization of the CLEC4C receptor and activates a signaling pathway that suppresses the production of type I interferons, such as IFN-alpha and IFN-beta, as well as other inflammatory cytokines and chemokines (PubMed: 36069818, PubMed: 32726550).