C-type lectin domain family 5 member A receptor (CLEC5A)

C-type lectin domain family 5 member A (CLEC5A), also known as MDL-1, is a type II transmembrane receptor expressed on myeloid cells [UniProt, Q9NY25]. It plays a critical role in the innate immune response by acting as a signaling receptor that associates with the DAP12 adapter protein [Teng et al., 2017]. CLEC5A is a key mediator of the "cytokine storm" in several viral infections, including Dengue and Influenza, where its activation leads to excessive inflammation and vascular leakage [Chen et al., 2008; Sung & Hsieh, 2021]. It is also implicated in the pathogenesis of autoimmune diseases like rheumatoid arthritis [Teng et al., 2017]. Therapeutic strategies targeting CLEC5A include monoclonal antibodies and RNA-based inhibitors designed to mitigate hyper-inflammatory responses [Teng et al., 2017; Sung & Hsieh, 2021].

Other names

MDL-1MDL1CLECSF5Myeloid DAP12-associating lectin-1

The mechanism of action involves blocking the interaction between the CLEC5A receptor and its ligands (such as the Dengue virus E protein) using monoclonal antibodies [Chen et al., 2008]. This prevents the activation of the associated DAP12 adapter protein and the subsequent ITAM-mediated signaling pathway, thereby inhibiting the release of pro-inflammatory cytokines [Teng et al., 2017]. Additionally, targeting the CLEC5A mRNA with siRNA or antisense oligonucleotides can reduce receptor expression at the translational level [Teng et al., 2017; Sung & Hsieh, 2021].