Psoriasis triggered by toll-like receptor 7 agonist imiquimod in the presence of dermal plasmacytoid dendritic cell precursors.
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.


METHODS
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.
Gilliet
Michel
M
Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland. m.gilliet@der.usz.ch
Conrad
Curdin
C
Geiges
Michael
M
Cozzio
Antonio
A
Thürlimann
Wolfgang
W
Burg
Günter
G
Nestle
Frank O
FO
Dummer
Reinhard
R
D000287:Administration, Topical; D000634:Aminoquinolines / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001706:Biopsy; D003713:Dendritic Cells / Q000473:pathology; D003951:Diagnostic Errors; D005455:Fluorescent Antibody Technique; D006801:Humans; D000077271:Imiquimod; D007150:Immunohistochemistry; D007369:Interferon Inducers / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008562:Membrane Glycoproteins / Q000819:agonists*; D008875:Middle Aged; D010950:Plasma Cells / Q000473:pathology; D011565:Psoriasis / Q000188:drug therapy* / Q000473:pathology*; D011956:Receptors, Cell Surface / Q000819:agonists*; D012867:Skin / Q000473:pathology*; D013234:Stem Cells / Q000473:pathology; D051199:Toll-Like Receptor 7; D051193:Toll-Like Receptors
D000634:Aminoquinolines; D007369:Interferon Inducers; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495348:TLR7 protein, human; D051199:Toll-Like Receptor 7; D051193:Toll-Like Receptors; D000077271:Imiquimod