Seif Farhad, Ghalehbaghi Babak, Aazami Hossein, Mohebbi Alireza, Ahmadi Aslan, Falak Reza, Babaheidarian Pegah, Najafi Mohammad, Khoshmirsafa Majid, Ghalehbaghi Sahand, Shekarabi Mehdi
1Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
2ENT and Head and Neck Research Center and Department, Hazrat Rasoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran.
Allergy Asthma Clin Immunol. 2018 Jul 5;14:47. doi: 10.1186/s13223-018-0270-9. eCollection 2018.
Chronic Rhinosinusitis (CRS) is a persistent inflammatory disease affecting paranasal sinuses. CRS is categorized into two distinct subgroups defined as CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). Although several immune cells are involved in the CRS pathogenesis, the role of T cells is not fully understood. The objective of the present study was to evaluate the frequency of CD4 and CD8 T cells and macrophages in the sinonasal mucosa of CRS patients, as well as to investigate the specific transcription factors for Th1, Th2, Th17, and Treg cells.
In this study, 15 healthy controls, 12 CRSsNP, and 23 CRSwNP patients participated. CD4, CD8, and CD68 cells were investigated in the sinonasal tissues using immunohistochemistry. The expression of transcription factors related to Th subsets (T-bet, GATA3, Ror-γt, and FoxP3) was evaluated using real-time PCR. Furthermore, CRSwNP patients were defined as eosinophilic when eosinophils consisted of more than 10% of total inflammatory cells. The Kruskal-Wallis, Mann-Whitney, and Spearman tests were used in statistical analyses.
The median (range) age of the studied groups was: 32 (14-67) for CRSwNP, 28 (10-43) for CRSsNP, and 27 (17-44) for controls. The number of eosinophils in CRSwNP patients was higher than two other groups, whereas neutrophils were elevated in both CRSwNP and CRSsNP groups in comparison to controls. The frequency of CD4 and CD8 T cells, macrophages, and total inflammatory cells were significantly increased in CRSwNP and CRSsNP patients compared with controls. The mRNA expression of GATA3 was increased in CRSwNP patients while mRNA expression of Ror-γt was elevated in CRSsNP patients. No significant difference was observed in T-bet mRNA expression among three groups. Both CRSwNP and CRSsNP patients showed decreased FoxP3 mRNA expression in comparison to controls.
The frequency of CD4 and CD8 T cells was elevated in CRS patients. In addition, we demonstrated Th2 dominance in CRSwNP patients and Th17 dominance in CRSsNP patients, implicating different mechanisms may underlie the disease. Better CRS classification and targeted therapeutic strategies may be achievable by determining the pattern of infiltrating inflammatory cells. Therefore, further experimental investigations on T cells are needed.
慢性鼻-鼻窦炎（CRS）是一种影响鼻窦的持续性炎症性疾病。CRS可分为两个不同的亚组，即伴鼻息肉的慢性鼻-鼻窦炎（CRSwNP）和不伴鼻息肉的慢性鼻-鼻窦炎（CRSsNP）。尽管几种免疫细胞参与了CRS的发病机制，但T细胞的作用尚未完全明确。本研究的目的是评估CRS患者鼻窦黏膜中CD4和CD8 T细胞及巨噬细胞的频率，并研究Th1、Th2、Th17和调节性T（Treg）细胞的特异性转录因子。
本研究纳入了15名健康对照者、12名CRSsNP患者和23名CRSwNP患者。采用免疫组织化学法检测鼻窦组织中的CD4、CD8和CD68细胞。使用实时聚合酶链反应（PCR）评估与Th亚群相关的转录因子（T-bet、GATA3、ROR-γt和FoxP3）的表达。此外，当嗜酸性粒细胞占总炎症细胞的比例超过10%时，CRSwNP患者被定义为嗜酸性粒细胞性。统计分析采用Kruskal-Wallis检验、Mann-Whitney检验和Spearman检验。
研究组的中位（范围）年龄为：CRSwNP组32岁（14 - 67岁），CRSsNP组28岁（10 - 43岁），对照组27岁（17 - 44岁）。CRSwNP患者的嗜酸性粒细胞数量高于其他两组，而与对照组相比，CRSwNP组和CRSsNP组的中性粒细胞均升高。与对照组相比，CRSwNP组和CRSsNP组患者的CD4和CD8 T细胞、巨噬细胞及总炎症细胞的频率显著增加。CRSwNP患者中GATA3的mRNA表达增加，而CRSsNP患者中ROR-γt的mRNA表达升高。三组之间T-bet mRNA表达未观察到显著差异。与对照组相比，CRSwNP组和CRSsNP组患者的FoxP3 mRNA表达均降低。
CRS患者中CD4和CD8 T细胞的频率升高。此外，我们证明CRSwNP患者以Th2为主，CRSsNP患者以Th17为主，这表明该疾病可能存在不同的发病机制。通过确定炎症细胞浸润模式，可能实现更好的CRS分类和靶向治疗策略。因此，需要对T细胞进行进一步的实验研究。
