C-Type Lectin Receptor Mediated Modulation of T2 Immune Responses to Allergens

Allergic diseases represent a major health problem of increasing prevalence worldwide. In allergy, dendritic cells (DCs) contribute to both the pathophysiology and the induction of healthy immune responses to the allergens. Different studies have reported that some common allergens contain glycans in their structure. C-type lectin receptors (CLRs) expressed by DCs recognize carbohydrate structures and are crucial in allergen uptake, presentation, and polarization of T cell responses. This review summarizes the recent literature regarding the role of CLRs in the regulation of type 2 immune responses to allergens.

In this review, we highlight the capacity of CLRs to recognize carbohydrates in common allergens triggering different signaling pathways involved in the polarization of CD4⁺ T cells towards specific Th2 responses. Under certain conditions, specific CLRs could also promote tolerogenic responses to allergens, which might well be exploited to develop novel therapeutic approaches of allergen-specific immunotherapy (AIT), the single treatment with potential disease-modifying capacity for allergic disease. At this regard, polymerized allergens conjugated to non-oxidized mannan (allergoid-mannan conjugated) are next-generation vaccines targeting DCs via CLRs that promote regulatory T cells, thus favoring allergen tolerance both in preclinical models and clinical trials. A better understanding of the role of CLRs in the development of allergy and in the induction of allergen tolerance might well pave the way for the design of novel strategies for allergic diseases.