Major differences in inflammatory dendritic cells and their products distinguish atopic dermatitis from psoriasis

Requirement of CCL17 for CCR7- and CXCR4-dependent migration of cutaneous dendritic cells

“…Consistent with our findings in the mouse model, the number of epidermal LCs is reduced in lesional skin of AD patients compared with normal skin, and LC migration from the epidermis to the dermis correlates with enhanced expression of thymic stromal lymphopoietin (TSLP) in the epidermis (40,41). In this context, it is interesting to note that TSLP induces maturation and CCL17 expression in DCs.…”

Expression and Function of CCL17 in Atopic Dermatitis

“…The main conclusion from these experiments is that CCL17 contributes to the pathogenesis of AD in two different ways: i) upregulation of the inflammatory chemokine CCL17 in cutaneous DC is essential for LC emigration from the skin and thus for priming of immune responses in the draining LN, and ii) CCL17 (together with other chemokines, such as CCL22 and CCL27) enhances the attraction of activated T cells from the circulation to the inflamed skin. Our finding on the role of CCL17 in the induction of LC emigration is in line with histological observations in the skin of AD patients that expression of TSLP, a major inducer of CCL17, correlates with enhanced migratory activity of LC (Guttman-Yassky et al, 2007;Soumelis et al, 2002). Already in 2001, Katou et al reported that about 50% of LC in inflamed skin but not dermal DC express the CCR4 receptor, suggesting that CCR4 ligands also influence LC migration (Katou et al, 2001).…”

“…Interestingly, the keratinocyte-derived cytokine TSLP, which is strongly upregulated in the epidermis of AD lesional skin specifically induces CCL17 and CCL22 expression in human peripheral blood CD11c + DC (Soumelis et al, 2002) as well as human epidermal LC (Ebner et al, 2007). TSLP expression levels in the skin also correlated with enhanced migratory activity of LC (Guttman-Yassky et al, 2007;Soumelis et al, 2002). A possible link between skin barrier dysfunction and CCL17 was recently reported by Nakahigashi et al, who showed that CCL17 was able to induce aquaporin-3 in human keratinocytes, which in turn promoted keratinocyte proliferation and disturbed barrier function (Nakahigashi et al, 2010).…”

Langerin neg conventional dendritic cells produce IL-23 to drive psoriatic plaque formation in mice

“…Previous studies reported an essential role for pDCs in the initiation of psoriasis as they transiently infiltrate early lesions and flare-ups of psoriasis upon topical application of Aldara/IMQ (2,8). Established psoriasis lesions however, lack this marked influx of pDCs, suggesting a sequential role for different DC populations during cutaneous disease (22,27,28). DCs are not only crucial to maintain immune homeostasis at epithelial borders including the skin, they are also the central link between innate and adaptive immunity.…”