Cho Soo-Na, Song Chang-Hwa, Jin Jun, Kim Sung Ha, Rha Ki-Sang, Kim Yong Min
Department of Microbiology, Chungnam National University School of Medicine, Daejeon, Korea.
Am J Rhinol Allergy. 2014 Jan-Feb;28(1):e17-24. doi: 10.2500/ajra.2014.28.3995.
The pathogenesis of nasal polyposis has not been fully understood. Recent studies indicate that there is a subset of CD4(+)CD25(high)FoxP3(+)T cells (regulatory T cells [Tregs]) that express retinoic acid receptor related orphan receptor C (RORC) or IL-17, and these cells might be new proinflammatory cells because of the expression of IL-17 with loss of their suppressive function. The goals of this study were to localize Th17-like Tregs (Th17-like Tregs or RORC(+)Tregs) in nasal polyps and to investigate the role of staphylococcal enterotoxin B (SEB) on the differentiation of Tregs to RORC(+)Tregs in vitro.
A total of 60 patients were enrolled in this study. Of the 60 patients, 40 had chronic rhinosinusitis with nasal polyps (CRSwNPs), and 20 subjects who were undergoing septoplasty were enrolled as control subjects. The nasal polyps of CRSwNP patients were subclassified as either eosinophilic polyp (EP) and noneosinophilic polyp (NEP) according to the result of hematoxylin and eosin stain. Tissues and whole blood were collected from all subjects. Double immunofluorescent staining and reverse-transcription polymerase chain reaction for RORC and FOXP3 were conducted on the tissues. RORC expressions of Tregs were measured in the tissue using flow cytometry. The proportions of RORC(+)Tregs subsets and cytokines profiles from the supernatant were measured using flow cytometry after stimulation with SEB.
The cells that express both RORC and FOXP3 and RORC(+)Tregs were significantly higher in the nasal polyps, especially in EPs compared with NEPs, and control mucosa. RORC(+)Tregs in peripheral blood mononuclear cells significantly increased in patients with EPs 24 hours after SEB stimulation in vitro.
The results indicate that SEB may be involved in the differentiation of Tregs to RORC(+)Tregs, and these cells may be involved in the pathogenesis of eosinophilic nasal polyposis.
鼻息肉的发病机制尚未完全明确。近期研究表明,存在一部分CD4(+)CD25(高)FoxP3(+)T细胞(调节性T细胞[Tregs])表达视黄酸受体相关孤儿受体C(RORC)或白细胞介素-17(IL-17),并且由于这些细胞表达IL-17且其抑制功能丧失,它们可能是新的促炎细胞。本研究的目的是在鼻息肉中定位Th17样调节性T细胞(Th17样调节性T细胞或RORC(+)调节性T细胞),并在体外研究葡萄球菌肠毒素B(SEB)对调节性T细胞向RORC(+)调节性T细胞分化的作用。
本研究共纳入60例患者。在这60例患者中,40例患有慢性鼻窦炎伴鼻息肉(CRSwNP),20例接受鼻中隔成形术的受试者作为对照。根据苏木精和伊红染色结果,将CRSwNP患者的鼻息肉分为嗜酸性粒细胞性息肉(EP)和非嗜酸性粒细胞性息肉(NEP)。从所有受试者收集组织和全血。对组织进行RORC和FOXP3的双重免疫荧光染色及逆转录聚合酶链反应。使用流式细胞术检测组织中调节性T细胞的RORC表达。用SEB刺激后,使用流式细胞术检测上清液中RORC(+)调节性T细胞亚群的比例和细胞因子谱。
与NEP和对照黏膜相比,鼻息肉中同时表达RORC和FOXP3的细胞以及RORC(+)调节性T细胞显著更高,尤其是在EP中。体外SEB刺激24小时后,EP患者外周血单个核细胞中的RORC(+)调节性T细胞显著增加。
结果表明,SEB可能参与调节性T细胞向RORC(+)调节性T细胞的分化,并且这些细胞可能参与嗜酸性粒细胞性鼻息肉的发病机制。