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SummaryRecent progress achieved by an impressive number of studies focusing upon the ontogenesis and immunobiology of epidermal Langerhans cells (LCs) and other cutaneous dendritic cell (DC) populations as well as DCs at oral mucosal tissue has profoundly revised our understanding of the role of DCs in different tissues and microenvironments. By sensing their environment for microbial signals or allergens and bridging innate and adaptive immunity in a sophisticated manner, subtypes of DCs play a critical role in the maintenance of the immunological homeostasis in the periphery. Thereby, DCs, located directly at the interface to the environment, fulfil opposing tasks as they are key players in both the control and the generation of allergic inflammation. Furthermore, it is under ongoing debate whether DCs attenuate or aggravate allergic inflammation. As a consequence, accumulated knowledge gained in this field within the last few years has provided an excellent basis for innovative therapeutic opportunities which tend to target specifically the multi-faceted properties of DCs at distinct anatomical sites.

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The skin represents a physical barrier, which is capable of protecting the body from damaging invaders. Moreover, the skin operates as an active immunological organ, harbouring a complex network of dendritic cells (DCs), which serve as a bridge between innate and adaptive immunity. Equipped with specific pattern recognition receptors (PRRs), DCs are able to capture, process and present antigens to naïve T cells in the skin draining lymph nodes, thereby inducing adaptive antigen-specific immunity. However, the outcome of the immune response is shaped by numerous factors including the DC subtype, maturation state of DCs, composition of PRRs expressed by DCs, type of pathogen as well as factors in the microenvironment. Thus, cutaneous DC subtypes are known to contribute to both, peripheral tolerance and the generation of allergic skin inflammation. Identifying the underlying mechanisms is a challenging task in understanding DC biology. Based on their functional diversity, cutaneous DCs might represent promising therapeutic targets, with the potential of down-modulating pro-inflammatory immune responses and inducing tolerogenic pathways, thereby ensuring the maintenance of tissue homeostasis and restoring the balance of dysregulated immune reactions in the context of allergic skin diseases. In this review, we summarize the versatile character of DC subtypes in human skin and highlight their phenotypic characteristics and role in allergic skin inflammation. In addition, we discuss current therapeutic approaches for the management of inflammatory skin diseases such as atopic dermatitis with the main focus on strategies targeting DCs. We point towards potential challenges, benefits, risks and limitations for the treatment of patients.