The plot thickens while the scope broadens: a holistic view on IL-17 in psoriasis and other inflammatory disorders
The plot thickens while the scope broadens: a holistic view on IL-17 in psoriasis and other inflammatory disorders
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DOI：
10.1111/exd.12541
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发表时间：
2014-11-01
影响因子：
3.6
通讯作者：
Schoen, Michael P.
中科院分区：
文献类型：
--
作者：
Schoen, Michael P.
银屑病是一个有启发性的例子，突出了我们对白细胞介素（IL）-17的病理生理功能的认识。IL-17 A是与这种和其他慢性炎性疾病的关键致病特征有关的主要同种型。几种靶向IL-17 A（阿基诺单抗，ixekizumab）或其IL-17 RC/RA受体（brodalumab）的单克隆抗体目前处于临床开发的后期阶段，它们已显示出令人印象深刻的疗效。虽然表皮细胞IL-17被认为主要来源于辅助性T细胞（Th）17，但最近几个研究小组的研究表明，银屑病病变中的其他细胞类型，如中性粒细胞和肥大细胞，是IL-17的丰富来源，因此推测其在疾病过程中的作用程度被低估。这种最近的范式转变为靶向IL-17功能的新型化合物在银屑病和其他炎症性疾病中的快速和强大功效提供了合理的解释，并提供了对这些疾病中复杂细胞因子网络的更全面的看法。
Psoriasis is an instructive example highlighting our growing knowledge about pathophysiological functions of interleukin (IL)-17. IL-17A is the predominant isoform implicated in key pathogenic features in this and other chronic inflammatory disorders. Several monoclonal antibodies targeting IL-17A (secukinumab, ixekizumab) or its IL-17RC/RA receptor (brodalumab) are currently in late stages of clinical development, where they have shown impressive efficacy. While the eponymous IL-17 has been thought to originate primarily from T helper (Th)17 cells, more recent investigations by several groups suggest that other cell types in psoriatic lesions, such as neutrophils and mast cells, are rich sources of IL-17, thus presumably contributing to the disease process to an as yet underestimated extent. This recent paradigm shift provides a plausible explanation for the rapid and strong efficacy of the novel compounds targeting IL-17 functions in psoriasis and other inflammatory disorders, and provide a more comprehensive view on the complex cytokine network in these conditions.