Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, 55131, Germany.
Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, 55131, Germany.
J Dermatol Sci. 2017 Sep;87(3):221-227. doi: 10.1016/j.jdermsci.2017.06.010. Epub 2017 Jun 15.
The cytokine IL-17 is now a target for an array of therapeutic monoclonal antibodies supposed to treat a variety of inflammatory diseases. The forerunner Secukinumab, an IL-17A neutralizing antibody, is meanwhile approved as first-line treatments for moderate-to-severe plaque psoriasis, and as second-line treatment for psoriatic arthritis and ankylosing spondylitis. Ixekizumab and Brodalumab, both also targeting the IL-17 pathway, were also recently approved by the FDA for plaque psoriasis. Using mice overexpressing IL-17A in a tissue of choice, we showed that the ectopic expression of this cytokine in keratinocytes resulted in a spontaneous and very strong form of psoriasis-like dermatitis. Interestingly, this model showed some typical comorbidities found in humans with psoriasis. In this review, we will discuss why IL-17 is a good target especially in psoriasis and what we learned from mouse models about its functions in pathological situations.
细胞因子 IL-17 现已成为一系列治疗性单克隆抗体的靶点,这些抗体旨在治疗多种炎症性疾病。前体药物 Secukinumab 是一种 IL-17A 中和抗体,现已被批准用于中重度斑块型银屑病的一线治疗,以及用于银屑病关节炎和强直性脊柱炎的二线治疗。同样针对 IL-17 通路的 Ixekizumab 和 Brodalumab 也最近被 FDA 批准用于斑块型银屑病。我们利用在特定组织中过表达 IL-17A 的小鼠,表明这种细胞因子在角质细胞中的异位表达导致了一种自发的、非常强烈的银屑病样皮炎。有趣的是,该模型显示了一些在人类银屑病中发现的典型合并症。在这篇综述中,我们将讨论为什么 IL-17 是一个很好的靶点,尤其是在银屑病中,以及我们从小鼠模型中学到的关于其在病理情况下的功能。