The Journal of Experimental Medicine
Tools for dendritic cell research
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 5 July 2005. doi:10.1084/jem.20050500
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 202, Number 1, 135-143
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Nestle, F. O.
Right arrow Articles by Gilliet, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nestle, F. O.
Right arrow Articles by Gilliet, M.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

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.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS