Vanderhaegen Thibault, Gengler Isabelle, Dendooven Arnaud, Chenivesse Cecile, Lefèvre Guillaume, Mortuaire Geoffrey
Otorhinolaryngology - Head and neck Department, Huriez Hospital, CHU Lille, Lille, France.
Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, 59000, Lille, France.
Clin Rev Allergy Immunol. 2022 Feb;62(1):90-102. doi: 10.1007/s12016-021-08844-7. Epub 2021 Jan 26.
Eosinophils are often considered as the pathologic landmark of chronic rhinosinusitis with nasal polyps (CRSwNP). Many studies emphasize their pivotal role in mucosal remodeling by their innate action via cytotoxic proteins degranulation. Eosinophil nasal recruitment from the bloodstream through endothelium diapedeses requires the intricate action between the nasal epithelium, epithelial cell-activated type 2 innate lymphoid cells, and adaptive immune cells secreting alarmins, cytokines, and specific chemokines. This immune pathway refers to a T-helper 2 (T2)-driven lymphocyte response, often considered as the main inflammatory process in CRSwNP in western countries. The release of T2 cytokines, among which interleukin (IL)-4, IL-5, and IL-13, fundamentally contributes to this immune response. New biologic agents capable of blocking T2 cytokines have been developed in the field of eosinophil-associated diseases, shifting the paradigm of treatment for patients with CRSwNP. The first part of this review describes each step of the eosinophil journey from hematopoietic stem cell maturation to nasal mucosa homing. The different eosinophil activation processes and their inflammatory functions are also described. This is followed by a discussion on currently available biologic therapies in CRSwNP with a specific focus on eosinophilic response. Beyond an eosinophil-blocking strategy, a cluster analysis of specific T2 biomarkers could be required to best predict the response to such biologic therapies in the future.
嗜酸性粒细胞常被视为伴鼻息肉的慢性鼻-鼻窦炎(CRSwNP)的病理标志。许多研究强调它们通过细胞毒性蛋白脱颗粒的固有作用在黏膜重塑中起关键作用。嗜酸性粒细胞从血液中通过内皮细胞渗出进入鼻腔需要鼻上皮、上皮细胞激活的2型固有淋巴细胞以及分泌警报素、细胞因子和特定趋化因子的适应性免疫细胞之间的复杂作用。这种免疫途径指的是由辅助性T细胞2(Th2)驱动的淋巴细胞反应,在西方国家通常被认为是CRSwNP中的主要炎症过程。Th2细胞因子的释放,其中包括白细胞介素(IL)-4、IL-5和IL-13,从根本上促成了这种免疫反应。在嗜酸性粒细胞相关疾病领域已开发出能够阻断Th2细胞因子的新型生物制剂,这改变了CRSwNP患者的治疗模式。本综述的第一部分描述了嗜酸性粒细胞从造血干细胞成熟到归巢至鼻黏膜的每个步骤。还描述了不同的嗜酸性粒细胞激活过程及其炎症功能。接下来讨论了CRSwNP中目前可用的生物疗法,特别关注嗜酸性粒细胞反应。除了嗜酸性粒细胞阻断策略外,未来可能需要对特定的Th2生物标志物进行聚类分析,以最好地预测对此类生物疗法的反应。