Dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) and Low affinity immunoglobulin epsilon Fc receptor (CD23) (DC-SIGN/CD23)

The target "DC-SIGN and CD23 – sialylation-dependent Fc binding" refers to a specialized immunomodulatory pathway where α2,6-sialylated IgG Fc fragments interact with specific C-type lectin receptors to exert anti-inflammatory effects (Anthony et al., 2008). DC-SIGN (CD209) and CD23 (FCER2) serve as the primary receptors for these sialylated glycans, which are naturally present on a small fraction of IgG molecules within pooled human intravenous immunoglobulin (IVIG) (Sondermann et al., 2013). Binding to these receptors initiates a signaling cascade that typically involves the release of interleukin-33 (IL-33), which subsequently induces interleukin-4 (IL-4) production by innate immune cells (Pincetic et al., 2014). This process culminates in the upregulation of the inhibitory receptor FcγRIIB on effector macrophages, thereby raising the threshold for inflammatory activation and suppressing autoantibody-mediated tissue damage (Schwab & Nimmerjahn, 2013). This pathway is a major focus for developing next-generation anti-inflammatory biologics, such as hypersialylated Fc fragments (e.g., M254), which aim to provide the therapeutic benefits of IVIG at significantly lower doses (Washburn et al., 2015).

Other names

CD209FCER2SIGN-R1CLEC4LBLAST-2Sialylated IgG Fc receptor

Agonism of DC-SIGN and CD23 by α2,6-sialylated IgG Fc fragments triggers an IL-33/IL-4 signaling cascade that upregulates the inhibitory receptor FcγRIIB on effector macrophages, thereby suppressing autoantibody-mediated inflammation.