Dendritic cells as orchestrators in the allergen-specific immunotherapy of allergic diseases

Dendritic cells (DCs) play a pivotal role in regulating immune responses, encompassing both tolerance and activation. Dysregulation of DC function is fundamental in the development of allergic conditions, underscoring their significance as a major focus for allergen-specific immunotherapy (AIT). This review systematically delineates the intricate landscape of DC subsets, comprising conventional DCs, plasmacytoid DCs, monocyte-derived DCs, and Langerhans cells, elucidating their specific contributions to either fostering Th2-driven inflammation or driving regulatory T cell generation. We dissect the multi-layered mechanisms through which DCs orchestrate immune tolerance, spanning cytokine signaling, metabolic reprogramming, epigenetic remodeling, and migratory dynamics. Additionally, the article extensively evaluates and contrasts the distinct roles of DC subsets and their modes of antigen presentation across various AIT administration routes (e.g. subcutaneous, sublingual, oral, epidermal, intranasal, intralymphatic and intratonsillar). Lastly, we highlight next-generation DC-targeted strategies, such as nanoparticle-mediated delivery systems and genetic engineering methodologies, designed to reprogram DCs toward a stable tolerogenic phenotype and enhance therapeutic efficacy. Translating these preclinical advances into personalized clinical interventions represents a pivotal frontier for establishing durable immune tolerance in allergic disorders.