Figure 2.

In vivo targeting of receptors on DCs against immunopathologies. Different receptors on dendritic cells (DCs) could be targeted using either antigen-antibody fusion compounds or carbohydrate-modified antigens. Brown arrows: the cDC1 and cDC2 subsets express a variety of receptors in both humans (purple boxes) and mice (blue boxes), which recognize and internalize fusion antibodies coupled with antigens, specific for a DC receptor and mediate the deletion of autoreactive T cells, induction of T cell anergy, generation of antigen-specific Foxp3⁺ Tregs and expansion of natural Tregs (These tolerogenic responses are abrogated if fusion antibodies are administered together with adjuvants like PolyI:C). The generation of either antigen-specific Foxp3⁺ Tregs or promotion of natural Tregs expansion depends of the receptor being targeted. Green arrows: Fusion antibodies against Siglecs, coupled with antigens or sialic acid-modified antigens bind to Siglec receptors on DCs and induce anti-inflammatory signals that result in the induction of Foxp3⁺ T cells, T cell anergy and the inhibition of Th1 responses. Red arrows: Targeting the MR, DC-SIGN and MGL on DCs with antigens conjugated to specific glycan moieties, result in the polarization of Th2 responses in allergy to Th1 responses and the induction of Foxp3⁺ T cells. Moreover, this interaction promotes the production of IgG4 blocking antibodies and mediates the reduction of IgE secretion. CLEC9A, C-type lectin domain family 9 member A; Treml4, The Triggering Receptor Expressed on Myeloid cells-like 4; DCIR, dendritic cell immunoreceptor; CLEC12A, C-type lectin domain family 12 member A; cDC1, Conventional type 1 dendritic cells; cDC2, Conventional type 2 dendritic cells; Siglec, Sialic acid-binding immunoglobulin-type lectins; MR, Mannose receptor; DC-SIGN, Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin; MGL, macrophage galactose-type C-type lectin. Langerin*: Induced expression.