Mainly, the tolerogenic functions of LCs in non-inflamed skin are based on their immature state, low migratory properties and low expression of co-stimulatory molecules, as well as release of proinflammatory soluble mediators [11]. Moreover, data from a murine model system using the receptor activator of nuclear factor kappa B (NF-kB) ligand (RANKL),

overexpressing keratinocytes showed that LCs down-regulate co-stimulatory molecule expression and induce regulatory T cells, click here thereby modulating the skin immune response and attenuating overactivation even in an inflamed state [12]. However, under some circumstances LCs might also lose their tolerogenic properties and induce immunogenic immune responses during inflammatory conditions. Several FcεRI-bearing subtypes

have been identified so far in human skin of AD patients. Concerning myeloid DCs, both CD207+/CD1a+, i.e. LCs Tanespimycin nmr as well as CD207–/CD1a+/FcεRI+ DCs, are located in the epidermis [13]. While low numbers of CD207+/CD1a+/FcεRI+DCs occur in the dermis, CD1c+/FcεRI+ DCs represent the major DC subpopulation of the dermal compartment [14]. DC subtypes expressing FcεRI in the skin and blood of AD patients are IgE receptor-bearing epidermal LCs, which predominate in non-lesional AD (Table 1). Further, a subtype of DC, which in contrast to LCs does not have any Birbeck granules but expresses the mannose receptor (CD206), MycoClean Mycoplasma Removal Kit the so-called inflammatory dendritic epidermal cells (IDEC), invades the skin in the acute phase and persists during the chronic phase of AD [15]. PDCs detectable in the epidermal skin of patients with psoriasis, lupus erythematodes or allergic contact dermatitis are almost absent in patients with AD [16]. We know from atopy patch test models that after allergen application to the skin, an eczematous skin reaction develops within 24–48 h in

sensitized patients. This mechanism is in addition to the induction and release of a plethora of chemokines in the upper part of the skin [17] and recruitment of inflammatory cell subtypes such as IDECs from their dermal and blood precursors [18]. The initial predominance of T helper type 2 (Th2) cytokines during the acute phase is attenuated and the amount of Th1 cytokines, in particular IFN-γ, increases [19]. Other exogenous trigger factors such as microbial antigens might lead to very similar recruitment mechanisms. During the flare-up phase of AD, epidermal LCs up-regulate their FcεRI and co-stimulatory and major histocompatibility complex (MHC) expression [18]. Furthermore, they release chemotactic factors, but prime naive T cells primarily into T cells of the Th2 type.