The IL-23-IL-17 pathway as a therapeutic target in axial spondyloarthritis.,Nature Reviews Rheumatology

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The IL-23-IL-17 pathway as a therapeutic target in axial spondyloarthritis.
Nature Reviews Rheumatology ( IF 29.4 ) Pub Date : 2019-09-24 , DOI: 10.1038/s41584-019-0294-7
Joachim Sieper ₁ , Denis Poddubnyy _{1,

2} , Pierre Miossec ₃

Affiliation

The cytokines IL-23 and IL-17 have an important role in the pathogenesis of, and as a therapeutic target in, both animal models of chronic inflammation and some human chronic inflammatory diseases. The traditional view is that a main source of IL-17 is T cells and that IL-17 production is under the control of IL-23. IL-17 inhibition has shown good efficacy in clinical trials for ankylosing spondylitis (AS), a subtype of axial spondyloarthritis (axSpA) characterized by radiographic evidence of sacroiliitis. On the basis of data from animal models, genetic studies and the investigation of tissue and blood samples from patients with AS, IL-23 had also been predicted to be important in the pathogenesis of this disease and was therefore considered a potential therapeutic target for axSpA. However, two placebo-controlled, double-blind clinical trials in axSpA of monoclonal antibodies directed against either the p40 protein or the p19 protein of the IL-23 molecule had clear negative results. These findings indicate that IL-23 and IL-17 are at least partly uncoupled in axSpA. Reasons as to why, when and how such an uncoupling might occur are discussed in this Review, with special reference to the unique microenvironment of the subchondral bone marrow in axSpA.

中文翻译：

IL-23-IL-17 通路作为中轴型脊柱关节炎的治疗靶点。

细胞因子 IL-23 和 IL-17 在慢性炎症的动物模型和一些人类慢性炎症性疾病的发病机制中具有重要作用，并作为治疗靶点。传统观点认为，IL-17 的主要来源是 T 细胞，IL-17 的产生受 IL-23 的控制。IL-17 抑制在强直性脊柱炎 (AS) 的临床试验中显示出良好的疗效，AS 是轴性脊柱关节炎 (axSpA) 的一种亚型，其特征是骶髂关节炎的放射学证据。根据来自动物模型的数据、遗传研究以及对 AS 患者组织和血液样本的调查，IL-23 也被预测在该疾病的发病机制中很重要，因此被认为是 axSpA 的潜在治疗靶点. 然而，两个安慰剂对照，在 axSpA 中针对 IL-23 分子的 p40 蛋白或 p19 蛋白的单克隆抗体的双盲临床试验具有明显的阴性结果。这些发现表明 IL-23 和 IL-17 在 axSpA 中至少部分分离。本综述讨论了为何、何时以及如何可能发生这种解偶联的原因，特别提到了 axSpA 中软骨下骨髓的独特微环境。

更新日期：2019-09-25

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