Department of Otolaryngology, Guangzhou Key Laboratory of Otorhinolaryngology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China.
Institute of Immunology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, China.
Inflamm Res. 2021 Jan;70(1):139-149. doi: 10.1007/s00011-020-01424-z. Epub 2020 Nov 23.
IL-17 plays essential roles in neutrophilic inflammation in the lower respiratory tract, however, the characteristics of local IL-17 T cells in nasal inflammatory mucosa are not fully understood. We investigated the roles of IL-17 T cells in regulating neutrophil infiltration and the effect of the mucosal microenvironment in modulating IL-17 T cell differentiation in CRSwNP tissues.
47 polyp tissues from chronic rhinosinusitis with nasal polyps (CRSwNP) patients without corticosteroid therapy and 26 tissues from healthy mucosa were obtained.
Immunohistochemistry and flow cytometry were used to analyze the neutrophil infiltration, local IL-17 T cell subsets, as well as cytokine producing profiles of IL-17 T cell; tissue homogenates were used to study neutrophil migration and IL-17 T cell differentiation.
Increase of IL-17 cells and IL-17 T cell subsets was significant in polyp tissues versus controls, IL-17 cell number was positively correlated with neutrophil infiltration; while homogenates from polyp tissues with high IL-17 promoted neutrophil migration in vitro. IL-17 response was found in polyp-derived T cells upon Staphylococcus aureus infection. IL-17 T cells were also down-regulated in polyps from patients treated with glucocorticoid steroids, and exhibited poly-functionality patterns in polyp tissues. Finally, IL-17 T cell differentiation could be induced by IL-23, and homogenates from polyps could enhance IL-17 T cell development.
This study determined a functional association of IL-17 T cells with neutrophils in CRSwNP, and revealed that polyp microenvironment could promote IL-17 T cell differentiation, suggesting a potential feedback role for IL-17 T cell development and local neutrophilic inflammation.
IL-17 在呼吸道下中性粒细胞炎症中起重要作用,然而,鼻腔炎症黏膜中局部 IL-17 T 细胞的特征尚未完全了解。我们研究了 IL-17 T 细胞在调节中性粒细胞浸润中的作用,以及黏膜微环境在调节 CRSwNP 组织中 IL-17 T 细胞分化中的作用。
47 例未经皮质类固醇治疗的慢性鼻-鼻窦炎伴鼻息肉(CRSwNP)患者的息肉组织和 26 例健康黏膜组织。
免疫组织化学和流式细胞术用于分析中性粒细胞浸润、局部 IL-17 T 细胞亚群以及 IL-17 T 细胞的细胞因子产生谱;组织匀浆用于研究中性粒细胞迁移和 IL-17 T 细胞分化。
与对照组相比,息肉组织中 IL-17 细胞和 IL-17 T 细胞亚群增加显著,IL-17 细胞数量与中性粒细胞浸润呈正相关;而来自 IL-17 高的息肉组织的匀浆在体外促进中性粒细胞迁移。金黄色葡萄球菌感染后发现息肉衍生 T 细胞中有 IL-17 反应。糖皮质激素治疗的患者息肉中的 IL-17 T 细胞也受到抑制,并在息肉组织中表现出多功能性模式。最后,IL-17 T 细胞分化可被 IL-23 诱导,而息肉匀浆可增强 IL-17 T 细胞发育。
本研究确定了 CRSwNP 中 IL-17 T 细胞与中性粒细胞之间的功能关联,并表明息肉微环境可促进 IL-17 T 细胞分化,提示 IL-17 T 细胞发育和局部中性粒细胞炎症存在潜在的反馈作用。