The emerging role of IL-23 in asthma and its clinical implications.
The emerging role of IL-23 in asthma and its clinical implications.
复制标题
IL-23 在哮喘中的新作用及其临床意义。
DOI：
10.1080/1744666x.2023.2125380
复制
发表时间：
2023
影响因子：
4.4
通讯作者：
Peebles,RStokes
中科院分区：
文献类型：
--
作者：
Wu,AshleyY;Peebles,RStokes
哮喘是一种常见的慢性炎症性呼吸道疾病，其特征是气道高反应性（AHR）、异常粘液产生和气道平滑肌重塑。传统上，哮喘被认为是一种过敏性疾病，其特征在于“2型”炎性细胞的浸润，所述炎性细胞包括嗜酸性粒细胞、肥大细胞、嗜碱性粒细胞、CD 4 + T辅助2（Th 2）细胞和第2组先天性淋巴样细胞（ILC 2）。这些细胞通过典型的2型炎性细胞因子如白细胞介素（IL）-4，IL-5和IL-13介导过敏性炎症反应。越来越多的人认识到哮喘是一种临床异质性疾病，无论是在表型表现方面还是在炎症的分子基础方面，类固醇无反应患者的亚群主要是嗜酸性粒细胞性炎症，而不是嗜酸性粒细胞性炎症。鉴于传统抗2型炎症治疗难治的患者缺乏治疗选择，因此迫切需要针对导致哮喘严重程度的替代途径的治疗，既往临床前研究表明IL-23在哮喘发病机制中的潜在作用，观察性研究描述了血清IL-23水平与儿童哮喘严重程度的相关性[1-6]。在哮喘小鼠模型中，IL-23阻断导致气道炎症减少。在靶向分子治疗的时代，调节IL-23及其相关的下游IL-23/CD 4 + T辅助细胞17（Th 17）轴作为哮喘治疗的新靶点引起了强烈的兴趣。美国食品药品监督管理局（FDA）已经批准多种药物用于治疗Th 17介导的疾病，如炎症性肠病和银屑病（表1），但尚未证明它们在哮喘和其他特应性疾病中有效[7]。不幸的是，现有的动物模型数据和最近的人类研究迄今为止产生了相互矛盾和令人失望的结果。然而，更好地了解IL-23和哮喘中可见的气道炎症之间的复杂相互作用可能为未来的治疗铺平道路。
Asthma is a prevalent, chronic inflammatory respiratory disease defined by airway hyperresponsiveness (AHR), aberrant mucus production, and airway smooth muscle remodeling. Classically, asthma is considered an allergic disease, characterized by infiltrates of ‘type 2’inflammatory cells including eosinophils, mast cells, basophils, CD4+ T helper 2 (Th2) cells, and group 2 innate lymphoid cells (ILC2s). These cells mediate an allergic inflammatory response via canonical type 2 inflammatory cytokines such as interleukin (IL)-4, IL-5, and IL-13. Increasingly, asthma is recognized as a clinically heterogenous disease–both in terms of phenotypic presentation as well as molecular basis of inflammation–with subsets of steroid-unresponsive patients that have predominantly neutrophilic, rather than eosinophilic, inflammation. Given the paucity of treatment options for those who are refractory to traditional anti-type 2 inflammatory therapies, there is a dire need for therapies targeting alternative pathways that contribute to asthma severity.Prior preclinical studies demonstrate a potential role for IL-23 in asthma pathogenesis, and observational studies describe the association of serum IL-23 levels with asthma severity in children [1–6]. In mouse models of asthma, IL-23 blockade results in reduced airway inflammation. In the era of targeted molecular therapies, there is intense interest in modulating IL-23 and its related downstream IL-23/CD4+ T helper 17 (Th17) axis as a novel target for asthma therapy. Multiple agents are already approved by the United States Food and Drug Administration (FDA) for the treatment of Th17-mediated diseases such as inflammatory bowel disease and psoriasis (Table 1), but they have yet to be proven to be efficacious in asthma and other atopic diseases [7]. Unfortunately, existing animal model data and recent human studies have thus far yielded conflicting and disappointing results. However, a better understanding of the complex interplay between IL-23 and airway inflammation seen in asthma may yet pave the way for future therapies.