Exploring Siglecs: Potential Modulators of Immune Cells in Food Allergy and Therapeutic Applications

Food allergies (FAs) are common in society with limited treatment options available. Therefore, there is an urgent need for new targets and treatment options. Sialic acid-binding immunoglobulin-type lectins (Siglecs) are mostly inhibitory receptors differentially expressed on all immune cells. There are many different types of Siglecs, and they are involved in the regulation of several signalling pathways. The specific role that Siglecs can have on various diseases, including cancer and immune-driven disorders, is gaining interest. This review focusses on the current knowledge of the role of Siglecs on immune cells involved in FA sensitisation and elicitation and how targeting these Siglecs could possibly prevent or treat FA. Most research is focussed on targeting Siglecs expressed by mast cells and basophils, and how this can dampen the activation and/or degranulation of these cells. Targeting Siglecs on cells involved in the sensitisation phase of FA could be an interesting option to intervene earlier on in the allergic response, thus preventing the onset of FA rather than treating it. Siglec-2 on B cells is already of great interest for the treatment of FA, and results seem promising as B cell receptor signalling and antibody production were inhibited. Siglecs on other cell types in the sensitisation phase, such as dendritic cells, seem promising, but functional assays with human cells are lacking so far. Overall, Siglecs are broadly expressed on all immune cells involved in the allergic response, which support the hypothesis that Siglecs are involved in the allergic response itself and may act as a potential target in the treatment of FA. Especially, treatments focussed on targeting Siglecs on multiple immune cell types may have great potential, as this could enhance both efficacy and safety.