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. Author manuscript; available in PMC: 2015 Oct 1.
Published in final edited form as: Nat Rev Immunol. 2014 Sep 19;14(10):653–666. doi: 10.1038/nri3737

Figure 4. Therapeutic potential of targeting Siglecs in disease.

Figure 4

(a) The endocytic property of the Siglecs expressed on lymphoma/leukemia cells (CD22/CD33) or macrophages (sialoadhesin) has been exploited to deliver cargo to the cell type of interest. Toxin or antigens can be delivered via conjugated anti-Siglec antibodies (left) or encapsulated in the lumen of liposomes displaying high affinity Siglec ligands (right). Once endocytosed, toxins are released to cause cell death, while antigens are loaded on MHC or CD1d for presentation to T cells and NKT cells, respectively. It is notable that in the case of targeting via glycan ligands, the modestly reduced endosomal pH is enough to cause dissociation ofSiglecs and their cargo, which allows for recycling of the Siglecs to the cell surface for additional rounds of cargo uptake. (b) Siglec-engaging tolerance-inducing antigenic liposomes (STALs) display both antigen and a high affinity ligand of the B cell Siglecs (CD22 and Siglec-G). STALs enforce association of the Siglecs with the BCR on B cells, inhibiting B cell activation that otherwise occurs when ligands are absent. Through downstream signaling events, a pro-apoptotic signal is delivered that results in apoptosis of the antigen-specific B cells, resulting in antigen-specific B cell tolerance.