World Allergy Forum: The Epithelium as a Modulator of the Allergic Response
Antigen Presenting Cells in the Skin
The skin represents the main interface organ directly in contact with the environment. Here, at the very border of our entire organism, the immunologic properties of the skin, our largest organ, are of vital importance. Several elements are crucial to fulfill these functions of the skin organ. The skin immune system (SIS)(1) is an organ-related unit of this complex network which has to fulfill a variety of protective and effector functions due to the interface status of the skin.
Besides the static celllular components, i.e. keratinocytes, fibroblasts and endothelial cells, the more dynamic cellular component includes leucocytes, i.e. T lymphocytes, macrophages, Langerhans cells and other dendritic cells which are committed to spend a limited time in the skin. The latters are highly specialized professional antigen presenting cells which have a crucial role to play in physiological and pathophysiological events. In the epidermal compartment, the paradigmatic dendritic cells, i.e. the Langerhans cells, are known to be essential for the induction of primary immune responses toward various kinds of potential dangerous agents (2) as non-self (e.g. haptens, proteinic allergens)(3) or self structures (e.g. tumor antigens).
Most recent research work has focused on the mechanisms leading to the colonization of the skin by these APC directed by distinct chemokines as MIP-3. Some findings have questioned whether LC are also responsible for the induction of a secondary immune response at the skin level, i.e. an allergic contact dermatitis. Thus, there is some evidence that professional APC in the dermal compartment, i.e. macrophages and the heterogeneous family of dermal dendritic cells could be responsible for triggering cell-mediated inflammatory reactions.
Furthermore, during these conditions, it is postulated that APC migrate in both directions, leading to the presence of a mixture of APC, particularly in the epidermis in the context of allergic contact dermatitis, atopic eczema or after UV-irradiation. Whether these cell movements are part of a distinct cellular programm aimed to regulate the inflammatory reaction at each level remains to be clarified. Finally, progress in the immunbiology of skin APC will potentially lead to the development of new therapeutical tools aimed to specifically target these cells for either suppress/modulate their function (in the case of hypersensitivity reactions) or in contrast to strength their primary biological function, e.g. in the context of anti-tumoral strategies.
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