Dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) (DC-SIGN)

Dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), also known as CD209, is a type II transmembrane C-type lectin receptor primarily expressed on dendritic cells and certain macrophage populations [4, 9]. It serves a dual role as an adhesion molecule, mediating interactions with T cells via ICAM-3 and endothelial cells via ICAM-2, and as a pattern recognition receptor that captures diverse pathogens such as HIV-1, Ebola virus, SARS-CoV-2, and Mycobacterium tuberculosis [10, 12]. While its physiological function involves the internalization and processing of antigens for presentation to T cells, many pathogens exploit DC-SIGN to facilitate their own entry or dissemination through a process called trans-infection [11, 12]. In the context of oncology, DC-SIGN is frequently expressed on immunosuppressive M2-like tumor-associated macrophages, where it contributes to tumor progression and immune evasion [13, 15]. Therapeutic development focuses on glycomimetic inhibitors to block pathogen binding and the use of DC-SIGN-targeted delivery systems, such as pullulan nanoparticles, to enhance the efficacy of vaccines and immunotherapies [13, 40]. However, the structural similarity between DC-SIGN and related lectins like L-SIGN poses challenges for achieving high target specificity and avoiding potential safety concerns related to immune modulation [12, 40].

Other names

CD209CLEC4LSIGNR1CD209bDC-SIGNR1HIV gp120-binding protein

Inhibition of pathogen binding to block viral/bacterial entry and trans-infection; targeted antigen delivery to dendritic cells for enhanced vaccine efficacy; modulation of immune signaling through crosstalk with Toll-like receptors.