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Michel Gilliet, MD; Curdin Conrad, MD; Michael Geiges, MD; Antonio Cozzio, MD, PhD; Wolfgang Thürlimann, MD; Günter Burg, MD; Frank O. Nestle, MD; Reinhard Dummer, MD

Arch Dermatol. 2004;140:1490-1495.

Background  It has been proposed that the innate immune system plays a central role in driving the autoimmune T-cell cascade leading to psoriasis; however, there is no direct evidence for this.

Observations  We observed aggravation and spreading of a psoriatic plaque when treated topically with the toll-like receptor (TLR) 7 agonist imiquimod. The exacerbation of psoriasis was accompanied by a massive induction of lesional type I interferon activity, detected by MxA expression after imiquimod therapy. Since imiquimod induces large amounts of type I interferon production from TLR7-expressing plasmacytoid dendritic cell precursors (PDCs), the natural interferon-producing cells of the peripheral blood, we asked whether PDCs are present in psoriatic skin. We identified high numbers of PDCs in psoriatic skin lesions (up to 16% of the total dermal infiltrate) based on their coexpression of BDCA2 and CD123. By contrast, PDCs were present at very low levels in atopic dermatitis and not detected in normal human skin.

Conclusions  This study shows that psoriasis can be driven by the innate immune system through TLR ligation. Furthermore, our finding that large numbers of PDCs infiltrate psoriatic skin suggests a role of lesional PDCs as type I interferon-producing targets for the TLR7 agonist imiquimod.

Author Affiliations: Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland (Drs Gilliet, Conrad, Geiges, Cozzio, Burg, Nestle, and Dummer); Dr Thürlimann is in private practice in Zurich.

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