The sialic acid-binding immunoglobulin-type lectin family of cell adhesion receptors called Siglecs comprise 14 members in humans and 9 members in mice that are predominately expressed on white blood cells of the immune system. Many siglecs carry regulatory motifs that can regulate receptors involved in mediating immune responses, and help the immune system distinguish between self and non-self. We have developed a liposomal nanoparticle platform that exploits the inhibitory functions of siglecs for suppression of antigen induced immune cell activation. Key to this platform are synthetic ligands that bind with high avidity and high specificity for a single Siglec. The tolerogenic nanoparticles display an antigen and a ligand of an inhibitory Siglec expressed on the cells that recognize the antigen. When an immune cell receptor recognizes the antigen, the Siglecs are recruited to the immunological synapse, suppressing the immune response and effectively inducing tolerance to the antigen. These siglec ligand-decorated antigenic nanoparticles show potential for suppression of antigen-mediated immune responses of B cells and mast cells. (NIH grants AI050143, AI099141, HL107151).

Siglecs: Putting the brakes on the immune system

255th National Meeting (2018)

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