银屑病
免疫学
先天免疫系统
干扰素
α-干扰素
浆细胞样树突状细胞
生物
医学
干扰素γ
Ⅰ型干扰素
免疫系统
树突状细胞
作者
Frank O. Nestle,Curdin Conrad,Adrian Tun-Kyi,Bernhard Homey,Michael Gombert,Onur Boyman,Günter Burg,Yongjun Liu,Michel Gilliet
摘要
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.
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