Putting together the psoriasis puzzle: an update on developing targeted therapies.
Putting together the psoriasis puzzle: an update on developing targeted therapies.
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DOI：
10.1242/dmm.009092
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发表时间：
2012-07
影响因子：
4.3
通讯作者：
Krueger JG
中科院分区：
文献类型：
--
作者：
Johnson-Huang LM;Lowes MA;Krueger JG
寻常型牛皮癣是一种慢性、使人衰弱的皮肤病，影响着全世界数百万人。目前还没有小鼠模型能够准确地再现该疾病的所有方面，但患者皮肤组织的可及性促进了银屑病发病机制中许多途径的阐明，并强调了免疫系统在该疾病中的重要性。这些发现的病理生理学相关性得到了遗传学研究的支持，这些研究发现了与NFκB激活、IL-23信号传导和T辅助17 （Th17）细胞适应性免疫反应相关基因的多态性，以及与表皮屏障相关的基因。最近开发的生物制剂选择性地靶向免疫系统的特定成分，对治疗牛皮癣非常有效。特别是，新兴的治疗方法集中在靶向il -23 - th17细胞轴上，一些阻断IL-17信号传导的药物在早期临床试验中显示出有希望的结果。这篇综述讨论了从小鼠和患者研究中获得的关于牛皮癣发病机制的经验教训，强调了t细胞靶向和细胞因子阻断治疗的临床试验结果如何澄清了我们对该疾病的理解。
Psoriasis vulgaris is a chronic, debilitating skin disease that affects millions of people worldwide. There is no mouse model that accurately reproduces all facets of the disease, but the accessibility of skin tissue from patients has facilitated the elucidation of many pathways involved in the pathogenesis of psoriasis and highlighted the importance of the immune system in the disease. The pathophysiological relevance of these findings has been supported by genetic studies that identified polymorphisms in genes associated with NFκB activation, IL-23 signaling and T helper 17 (Th17)-cell adaptive immune responses, and in genes associated with the epidermal barrier. Recently developed biologic agents that selectively target specific components of the immune system are highly effective for treating psoriasis. In particular, emerging therapeutics are focused on targeting the IL-23–Th17-cell axis, and several agents that block IL-17 signaling have shown promising results in early-phase clinical trials. This review discusses lessons learned about the pathogenesis of psoriasis from mouse-and patient-based studies, emphasizing how the outcomes of clinical trials with T-cell-targeted and cytokine-blocking therapies have clarified our understanding of the disease.
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