Unité Mixte AP-HP/Institut Pasteur, Institut Pasteur, Immunoregulation Unit, Paris, France.
Paris University, Department of Rheumatology-Hôpital Cochin. Assistance Publique-Hôpitaux de Paris, EULAR Center of Excellence, Paris, France.
Front Immunol. 2021 Jan 8;11:553742. doi: 10.3389/fimmu.2020.553742. eCollection 2020.
Spondyloarthritis (SpA) is a chronic inflammatory rheumatism characterized by inflammation of sacroiliac joints, peripheral joints, and spine. The Assessment of SpondyloArthritis Society describes three disease forms: axial (axSpA), peripheral, and enthesitic SpA. Each may be associated with extra-articular manifestations: psoriasis, inflammatory bowel disease, and acute anterior uveitis. Genome-wide association studies performed in axSpA and psoriatic arthritis (PsA) have shown a shared genetic background, especially the interleukin 23 (IL-23)/IL-17 pathway, which suggests pathophysiological similarities. The convincing positive results of clinical trials assessing the effect of secukinumab and ixekizumab (anti-IL-17A monoclonal antibodies) in axSpA and PsA have reinforced the speculated crucial role of IL-17 in SpA. Nevertheless, and obviously unexpectedly, the differential efficacy of anti-IL-23-targeted treatments between axSpA (failure) and PsA (success) has profoundly disrupted our presumed knowledge of disease pathogeny. The cells able to secrete IL-17, their dependence on IL-23, and their respective role according to the clinical form of the disease is at the heart of the current debate to potentially explain these observed differences in efficacy of IL-23/IL-17-targeted therapy. In fact, IL-17 secretion is usually mainly related to T helper 17 lymphocytes. Nevertheless, several innate immune cells express IL-23 receptor and can produce IL-17. To what extent these alternative cell populations can produce IL-17 independent of IL-23 and their respective involvement in axSpA and PsA are the crucial scientific questions in SpA. From this viewpoint, this is a nice example of a reverse path from bedside to bench, in which the results of therapeutic trials allow for reflecting more in depth on the pathophysiology of a disease. Here we provide an overview of each innate immunity-producing IL-17 cell subset and their respective role in disease pathogeny at the current level of our knowledge.
脊柱关节炎（SpA）是一种慢性炎症性风湿病，其特征为骶髂关节、外周关节和脊柱炎症。评估脊柱关节炎协会描述了三种疾病形式：中轴型（axSpA）、外周型和附着点炎型 SpA。每种疾病都可能与关节外表现相关：银屑病、炎症性肠病和急性前葡萄膜炎。在 axSpA 和银屑病关节炎（PsA）中进行的全基因组关联研究显示出共同的遗传背景，特别是白细胞介素 23（IL-23）/白细胞介素 17（IL-17）通路，这表明存在病理生理学相似性。评估 secukinumab 和 ixekizumab（抗 IL-17A 单克隆抗体）在 axSpA 和 PsA 中疗效的临床试验令人信服的阳性结果，加强了推测 IL-17 在 SpA 中的关键作用。然而，显然出人意料的是，抗 IL-23 靶向治疗在 axSpA（失败）和 PsA（成功）之间的疗效差异，深刻地扰乱了我们对疾病发病机制的假设性认识。能够分泌 IL-17 的细胞、它们对 IL-23 的依赖性以及根据疾病的临床形式各自的作用，是当前关于潜在解释这些观察到的 IL-23/IL-17 靶向治疗疗效差异的争论的核心。实际上，IL-17 的分泌通常主要与辅助性 T 细胞 17 （Th17）淋巴细胞有关。然而，有几种固有免疫细胞表达 IL-23 受体并能产生 IL-17。这些替代细胞群在多大程度上能够独立于 IL-23 产生 IL-17 及其在 axSpA 和 PsA 中的各自参与，是 SpA 中的关键科学问题。从这个角度来看，这是一个从床边到实验室的反向路径的很好例子，治疗试验的结果允许我们更深入地思考疾病的病理生理学。在这里，我们根据目前的知识水平，概述了每个产生 IL-17 的固有免疫细胞亚群及其在疾病发病机制中的各自作用。
