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Plasmacytoid predendritic cells initiate psoriasis through interferon-α production
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)-α–...
Autores principales: | , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2005
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212894/ https://www.ncbi.nlm.nih.gov/pubmed/15998792 http://dx.doi.org/10.1084/jem.20050500 |
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author | Nestle, Frank O. Conrad, Curdin Tun-Kyi, Adrian Homey, Bernhard Gombert, Michael Boyman, Onur Burg, Günter Liu, Yong-Jun Gilliet, Michel |
author_facet | Nestle, Frank O. Conrad, Curdin Tun-Kyi, Adrian Homey, Bernhard Gombert, Michael Boyman, Onur Burg, Günter Liu, Yong-Jun Gilliet, Michel |
author_sort | Nestle, Frank O. |
collection | PubMed |
description | 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)-α–producing cells, infiltrate the skin of psoriatic patients and become activated to produce IFN-α early during disease formation. In a xenograft model of human psoriasis, we demonstrate that blocking IFN-α signaling or inhibiting the ability of PDCs to produce IFN-α prevented the T cell–dependent development of psoriasis. Furthermore, IFN-α reconstitution experiments demonstrated that PDC-derived IFN-α 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-α represent potential early targets for the treatment of psoriasis. |
format | Text |
id | pubmed-2212894 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2005 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-22128942008-03-11 Plasmacytoid predendritic cells initiate psoriasis through interferon-α production Nestle, Frank O. Conrad, Curdin Tun-Kyi, Adrian Homey, Bernhard Gombert, Michael Boyman, Onur Burg, Günter Liu, Yong-Jun Gilliet, Michel J Exp Med Article 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)-α–producing cells, infiltrate the skin of psoriatic patients and become activated to produce IFN-α early during disease formation. In a xenograft model of human psoriasis, we demonstrate that blocking IFN-α signaling or inhibiting the ability of PDCs to produce IFN-α prevented the T cell–dependent development of psoriasis. Furthermore, IFN-α reconstitution experiments demonstrated that PDC-derived IFN-α 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-α represent potential early targets for the treatment of psoriasis. The Rockefeller University Press 2005-07-04 /pmc/articles/PMC2212894/ /pubmed/15998792 http://dx.doi.org/10.1084/jem.20050500 Text en Copyright © 2005, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Article Nestle, Frank O. Conrad, Curdin Tun-Kyi, Adrian Homey, Bernhard Gombert, Michael Boyman, Onur Burg, Günter Liu, Yong-Jun Gilliet, Michel Plasmacytoid predendritic cells initiate psoriasis through interferon-α production |
title | Plasmacytoid predendritic cells initiate psoriasis through interferon-α production |
title_full | Plasmacytoid predendritic cells initiate psoriasis through interferon-α production |
title_fullStr | Plasmacytoid predendritic cells initiate psoriasis through interferon-α production |
title_full_unstemmed | Plasmacytoid predendritic cells initiate psoriasis through interferon-α production |
title_short | Plasmacytoid predendritic cells initiate psoriasis through interferon-α production |
title_sort | plasmacytoid predendritic cells initiate psoriasis through interferon-α production |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212894/ https://www.ncbi.nlm.nih.gov/pubmed/15998792 http://dx.doi.org/10.1084/jem.20050500 |
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