The Journal of Experimental Medicine
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Published 5 July 2005. doi:10.1084/jem.20050500
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 202, Number 1, 135-143
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*Psoriasis
*Stem Cells
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ARTICLE

 Plasmacytoid predendritic cells initiate psoriasis through interferon-{alpha} production

Frank O. Nestle1, Curdin Conrad1, Adrian Tun-Kyi1, Bernhard Homey2, Michael Gombert2, Onur Boyman1, Günter Burg1, Yong-Jun Liu3, and Michel Gilliet1

1 Department of Dermatology, University Hospital of Zurich, 8091 Zurich, Switzerland
2 Department of Dermatology, Heinrich-Heine-University, 40225 Düsseldorf, Germany
3 Department of Immunology, M.D. Anderson Cancer Center, Houston, TX 77030

CORRESPONDENCE Michel Gilliet: mgilliet{at}mdanderson.org OR Frank O. Nestle: nestle{at}derm.unizh.ch

Psoriasis is one of the most common T cell–mediated autoimmune diseases in humans. Although a role for the innate immune system in driving the autoimmune T cell cascade has been proposed, its nature remains elusive. We show that plasmacytoid predendritic cells (PDCs), the natural interferon (IFN)-{alpha}–producing cells, infiltrate the skin of psoriatic patients and become activated to produce IFN-{alpha} early during disease formation. In a xenograft model of human psoriasis, we demonstrate that blocking IFN-{alpha} signaling or inhibiting the ability of PDCs to produce IFN-{alpha} prevented the T cell–dependent development of psoriasis. Furthermore, IFN-{alpha} reconstitution experiments demonstrated that PDC-derived IFN-{alpha} is essential to drive the development of psoriasis in vivo. These findings uncover a novel innate immune pathway for triggering a common human autoimmune disease and suggest that PDCs and PDC-derived IFN-{alpha} represent potential early targets for the treatment of psoriasis.

Abbreviations used: CLSM, confocal laser scanning microscopy; IDDM, insulin- dependent diabetes mellitus; IRF, IFN regulatory factor; PDC, plasmacytoid pre-DC; SLE, systemic lupus erythematosus; TLR, toll-like receptor.

M. Gilliet's present address is Dept. of Immunology, M.D. Anderson Cancer Center, Houston, TX 77030.


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