Plasmacytoid predendritic cells initiate psoriasis through interferon-alpha production.
Plasmacytoid predendritic cells initiate psoriasis through interferon-alpha production.
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DOI：
10.1084/jem.20050500
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发表时间：
2005-07-04
影响因子：
15.3
通讯作者：
Gilliet, Michel
中科院分区：
文献类型：
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作者：
Nestle, Frank O;Conrad, Curdin;Tun-Kyi, Adrian;Homey, Bernhard;Gombert, Michael;Boyman, Onur;Burg, Gunter;Liu, Yong-Jun;Gilliet, Michel
银屑病是人类最常见的T细胞介导的自身免疫性疾病之一。尽管已经提出了先天免疫系统在驱动自身免疫T细胞级联中的作用，但其性质仍然难以捉摸。我们发现，浆细胞样前树突状细胞（PDCs），天然的干扰素（IFN）-α-生产细胞，渗透银屑病患者的皮肤，并成为激活产生IFN-α在疾病形成的早期。在人类银屑病的异种移植模型中，我们证明阻断IFN-α信号传导或抑制PDCs产生IFN-α的能力可阻止银屑病的T细胞依赖性发展。此外，IFN-α重建实验表明，PDC衍生的IFN-α是体内驱动银屑病发展所必需的。这些发现揭示了一种触发常见人类自身免疫性疾病的新的先天免疫途径，并表明PDC和PDC衍生的IFN-α是治疗银屑病的潜在早期靶点。
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.