Plasmacytoid predendritic cells initiate psoriasis through interferon-alpha 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)-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.
Nestle
Frank O
FO
Department of Dermatology, University Hospital of Zurich, 8091 Zurich, Switzerland.
Conrad
Curdin
C
Tun-Kyi
Adrian
A
Homey
Bernhard
B
Gombert
Michael
M
Boyman
Onur
O
Burg
Günter
G
Liu
Yong-Jun
YJ
Gilliet
Michel
M
D000818:Animals; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007113:Immunity, Innate; D016898:Interferon-alpha / Q000096:biosynthesis*; D016899:Interferon-beta / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D018345:Mice, Knockout; D010950:Plasma Cells / Q000276:immunology* / Q000473:pathology; D011565:Psoriasis / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D015398:Signal Transduction; D016038:Skin Transplantation / Q000276:immunology / Q000473:pathology; D013234:Stem Cells / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology; D014183:Transplantation, Heterologous
D016898:Interferon-alpha; D016899:Interferon-beta