Psoriasis pathogenesis and the development of novel targeted immune therapies.
Psoriasis pathogenesis and the development of novel targeted immune therapies.
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DOI：
10.1016/j.jaci.2017.07.004
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发表时间：
2017-09
期刊：
影响因子：
--
通讯作者：
Krueger JG
中科院分区：
文献类型：
--
作者：
Hawkes JE;Chan TC;Krueger JG
银屑病是由免疫系统、银屑病相关易感基因、银屑病自身抗原和多种环境因素之间复杂的相互作用引起的。在过去的二十年中，研究已经明确表明，银屑病是一种真正的T细胞介导的疾病，主要由致病性T细胞驱动，这些T细胞响应于IL-23产生高水平的IL-17。IL-23/T17细胞轴在银屑病发展中的中心作用的发现导致了这种疾病的致病模型的重大范式转变。银屑病前期皮肤中IL-17的活化和上调在角质形成细胞中产生“前馈”炎症反应，其是自我放大的，并通过诱导表皮增生、表皮细胞增殖和白细胞亚群募集到皮肤中来驱动成熟银屑病斑块的发展。针对IL-17信号传导的单克隆抗体（阿基诺单抗，ixekizumab和brodalumab）和较新的IL-23 p19拮抗剂（tildrakizumab，guselkumab和risankizumab）的临床试验数据强调了这些细胞因子作为银屑病疾病主要驱动因素的核心作用。我们目前正在见证银屑病治疗和管理的转化革命。新兴的双特异性抗体提供了更好的疾病控制的潜力，而小分子药物可能提供未来使用生物制剂的替代品和成本更低的长期疾病管理。
Psoriasis is caused by a complex interplay between the immune system, psoriasis-associated susceptibility loci, psoriasis autoantigens, and multiple environmental factors. Over the last two decades, research has unequivocally shown that psoriasis represents a bona fide T-cell mediated disease primarily driven by pathogenic T-cells that produce high levels of IL-17 in response to IL-23. The discovery of the central role for the IL-23/T17 cell axis in the development of psoriasis has led to a major paradigm shift in the pathogenic model for this condition. The activation and upregulation of IL-17 in pre-psoriatic skin produces a “feed forward” inflammatory response in keratinocytes that is self-amplifying and drives the development of mature psoriatic plaques by inducing epidermal hyperplasia, epidermal cell proliferation, and the recruitment of leukocyte subsets into the skin. Clinical trial data for monoclonal antibodies against IL-17 signaling (secukinumab, ixekizumab, and brodalumab) and newer IL-23p19 antagonists (tildrakizumab, guselkumab, and risankizumab) underscore the central role of these cytokines as predominant drivers of psoriatic disease. We are currently witnessing a translational revolution in the treatment and management of psoriasis. Emerging bispecific antibodies offer the potential for even better disease control, while small molecule drugs may offer future alternatives to the use of biologics and less costly long-term disease management.
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DOI：
10.1073/pnas.91.20.9282
发表时间：
1994-09-27
影响因子：
11.1
作者：
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