Another, unique feature is their capability to prime naive
T cells and direct the nature of T cell responses. Fulfilling these different tasks, several DC subtypes can act either as ‘good guys’ or as ‘bad guys’ in allergic immune responses. Human DCs can be subdivided into two major subtypes, myeloid DCs (MDCs) and plasmacytoid DCs (PDCs). MDCs are localized in the peripheral tissue, the blood or secondary lymphoid LY2157299 purchase organs [2]. PDCs can be detected in the blood and lymphoid organs and are characterized by expression of the α-chain of the interleukin (IL)-3 receptor (CD123) and the blood-derived DC antigen (BDCA)-2. They are interferon (IFN)-producing cells recognizing viral antigens by Toll-like receptor (TLR)-7 and TLR-9 [2]. Variations of the DC character depend upon the subtype of DCs, the microenvironment, the quantitative and qualitative nature of other DC subtypes and cells in the environment and their cross-talk and interaction with DCs, the maturation stage Trametinib price of DCs, pattern of surface receptors, etc. Having these
many-sided properties of DCs in mind it is important to understand, in as detailed a manner as possible, how DCs manage to induce or accelerate allergic immune responses as well as which qualities enable them to attenuate or prevent allergic inflammation or, moreover, promote the development of allergen-specific tolerance. One of the most impressive examples for these variations are DCs which express the high-affinity receptor for immunoglobulin (Ig)E (FcεRI). Depending upon the context, i.e. cell type and location of FcεRI-bearing DCs, allergic immune responses can be promoted such as in atopic dermatitis (AD) [3], prevented, as thought for FcεRIpos oral mucosal DCs during sublingual immunotherapy [4], or functions involved in virus defence may be altered, as observed for FcεRIpos PDCs [5]. In this work we summarize the versatile character of FcεRIpos human DCs exemplified in the context of allergic immune reactions. Epidermal DCs, which comprise about 2–5% of all epidermal cells, belong in non-inflamed skin mainly to the classical Langerhans
cells (LCs) which are characterized by the Tacrolimus (FK506) so-called Birbeck granules, visible by electron microscopy as tennis racquet-shaped vesicles. The Birbeck granules are thought to be connected to the C-type lectin Langerin expressed by these cells and involved in antigen presentation [6]. LCs are derived from monocytes as their direct precursors and are localized in the basal and suprabasal layers of the upper epidermis, where they reside in an immature state without renewal for months [7]. Transforming growth factor (TGF)-β is required for their differentiation [8]. In healthy, non-inflamed skin, LCs represent the only epidermal DC type. To some extent, LCs are believed to be able to maintain a state of tolerance in the skin [9].