FIGURE 1.

Concept of transcutaneous immunotherapy with carbohydrate-formulated allergen nanoparticles. Carbohydrates (e.g. mannan) are activated by mild periodate treatment and coupled to primary amines of allergens by reductive amination, thereby cross-linking the allergens and forming neoglycoconjugate nanoparticles with shielded IgE epitopes. Such nanoparticles are applied to barrier-disrupted skin where they are taken up by epidermal Langerhans cells (LC) via C-type lectin recteptors (CLR) or diffuse into the dermal compartment, in which they can be captured by dermal dendritic cells (dDC). It is unclear whether and to what extent they directly activate skin resident T cells. LCs and dDCs migrate to skin-draining lymph nodes in which they can promote antiallergic T cell responses. The carbohydrate moiety of the nanoparticles shields the allergen from interaction with receptor-bound IgE on dermal mast cells, thereby avoiding local side-effects. Notably, certain epidermal cells, such as keratinocytes or γδ T cells, may promote TH2-licensing of dendritic cells upon barrier disruption. Stimulation of dendritic cells by suitable C-type lectin receptors and/or other innate receptors can be utilized to suppress innate TH2 induction in the upper skin layers. Modified with permission from [24] and [56^▪].