A comprehensive analysis of pattern recognition receptors in normal and inflamed human epidermis: upregulation of dectin-1 in psoriasis.

Department of Dermatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Journal of Investigative Dermatology (Impact Factor: 6.19). 11/2010; 130(11):2611-20. DOI: 10.1038/jid.2010.196
Source: PubMed

ABSTRACT Human epidermis plays an important role in host defense by acting as a physical barrier and signaling interface between the environment and the immune system. Pattern recognition receptors (PRRs) are crucial to maintain homeostasis and provide protection during infection, but are also causally involved in monogenic auto-inflammatory diseases. This study aimed to investigate the epidermal expression of PRRs and several associated host defense molecules in healthy human skin, psoriasis, and atopic dermatitis (AD). Using microarray analysis and real-time quantitative PCR, we found that many of these genes are transcribed in normal human epidermis. Only a few genes were differentially induced in psoriasis (CLEC7A (dectin-1), Toll-like receptor (TLR) 4, and mannose receptor C type 1 (MRC1)) or AD (MRC1, IL1RN, and IL1β) compared with normal epidermis. A remarkably high expression of dectin-1 mRNA was observed in psoriatic epidermis and this was corroborated by immunohistochemistry. In cultured primary human keratinocytes, dectin-1 expression was induced by IFN-γ, IFN-α, and Th17 cytokines. Keratinocytes were unresponsive, however, to dectin-1 ligands such as β-glucan or heat-killed Candida albicans, nor did we observe synergy with TLR2/TLR5 ligands. In conclusion, upregulation of dectin-1 in psoriatic lesions seems to be under control of psoriasis-associated cytokines. Its role in the biology of skin inflammation and infection remains to be explored.

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