C-type lectin domain family 4 member C (BDCA2) (BDCA2)

C-type lectin domain family 4 member C (BDCA2), also known as CD303, is a type II transmembrane glycoprotein expressed exclusively on human plasmacytoid dendritic cells (pDCs). It functions as a potent negative regulator of the innate immune response, specifically inhibiting the production of type I interferons (IFN-I) and other pro-inflammatory cytokines upon ligation. In autoimmune conditions such as systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE), pDCs are chronically activated, leading to an overproduction of IFN-I that drives systemic inflammation and tissue damage. Therapeutic strategies targeting BDCA2 utilize monoclonal antibodies, such as litifilimab (BIIB059), to bind the receptor and trigger its internalization. This process effectively dampens pDC activation and reduces the secretion of inflammatory mediators, thereby alleviating disease symptoms and preventing flares. Beyond lupus, BDCA2 is also being explored as a target in other interferon-mediated diseases like systemic sclerosis and certain hematologic malignancies.

Other names

Blood dendritic cell antigen 2CD303CLEC4CCLECSF11CLECSF7Dendritic lectinDLECHECL

Monoclonal antibody binding to BDCA2 leads to receptor internalization and subsequent inhibition of type I and III interferon and other pro-inflammatory cytokine production by plasmacytoid dendritic cells.