The Potential of Exosomes in Allergy Immunotherapy

Allergic diseases represent a global health and economic burden of increasing significance. The lack of disease-modifying therapies besides specific allergen immunotherapy (AIT) which is not available for all types of allergies, necessitates the study of novel therapeutic approaches. Exosomes are small endosome-derived vesicles delivering cargo between cells and thus allowing inter-cellular communication. Since immune cells make use of exosomes to boost, deviate, or suppress immune responses, exosomes are intriguing candidates for immunotherapy. Researchers from Sorbonne Université review the role of exosomes in allergic sensitization and inflammation, and they discuss the mechanisms by which exosomes could potentially be used in immunotherapeutic approaches for the treatment of allergic diseases. The researchers propose the following approaches: (a) Mast cell-derived exosomes expressing IgE receptor FcεRI could absorb IgE and down-regulate systemic IgE levels. (b) Tolerogenic exosomes could suppress allergic immune responses via induction of regulatory T cells. (c) Exosomes could promote TH1-like responses towards an allergen. (d) Exosomes could modulate IgE-facilitated antigen presentation.

Exosomes in allergic sensitization and inflammation

Allergic sensitization is thought to be driven by allergen entry through epithelium in a damaged or inflamed environment. Epithelial cells release TSLP/IL-33/IL-25 activating DCs and ILC2 cells which initiate type 2 immunity (TH2). Additionally, epithelial cells release exosomes containing contactin-1 (CNTN1) that play a role in recruiting macrophages and mo-DCs. DC-derived and B cell-derived exosomes containing allergen, p-MHCII complexes and co-stimulatory molecules can amplify the TH2 milieu. ILC2 cells activate and recruit eosinophils via IL-5 resulting in exosome release that promote ROS production in eosinophils and further eosinophil recruitment. Mast cell-derived exosomes can amplify TH2 responses by stimulating lymphocytes via co-stimulatory molecules, such as OX40L, LFA-1 and CD40L