Section of Otolaryngology-Head and Neck Surgery, Department of Surgery, The University of Chicago, Chicago, Illinois, USA.
Am J Rhinol Allergy. 2012 Sep-Oct;26(5):371-9. doi: 10.2500/ajra.2012.26.3800.
The pathogenesis of chronic rhinosinusitis (CRS) has not been fully elucidated. Increased inflammatory cell infiltration and decreased numbers and/or impaired function of T regulatory cells (Tregs) have been reported. This study aimed to determine the role of Tregs in CRS in peripheral blood (PB) and sinus tissue.
Sinus tissue was obtained from 16 CRS subjects and 5 controls. PB from additional 16 CRS subjects and total 20 controls was obtained. Immunohistochemical analysis (CD3(+), CD4(+), CD8(+), and Treg [CD4(+)-FoxP3(+) and CD25(+)-FoxP3(+)] cells) of sinus tissue was performed. Percentage of PB Tregs (CD4(+)-CD25(+)-FoxP3(+) cells) was analyzed by flow cytometry. Spontaneous and phytohemagglutinin (PHA)-induced release of cytokines (IL-6, IL-4, IL-10, interferon gamma, transforming growth factor [TGF] beta1, and TNF-alpha) from PB mononuclear cells (PBMCs) was determined.
PB flow cytometric analysis revealed a lower percentage of Tregs in subjects with CRS compared with healthy controls (p = 0.0003). Although no differences in the PB Treg counts were observed between the CRS subjects with nasal polyposis (CRSwNP) and without nasal polyposis (CRSsNP), immunohistochemical analysis performed on sinus tissue revealed a higher proportion of Tregs in CRSwNP subjects compared with CRSsNP (p < 0.05). Additionally, we failed to detect any Tregs from control sphenoid sinus tissue. Lower levels of regulatory cytokines (IL-10 and TGF-β1) and higher levels of proinflammatory cytokines (TNF-α and IL-6) were found from PBMCs from CRS subjects compared with controls (p < 0.05).
Our findings suggest that CRS subjects exhibit a decreased percentage of PB Tregs compared with normal controls. PBMCs from CRS subjects show a more proinflammatory and less regulatory phenotype.
慢性鼻-鼻窦炎(CRS)的发病机制尚未完全阐明。有报道称,炎症细胞浸润增加,T 调节细胞(Tregs)数量减少和/或功能受损。本研究旨在确定 Tregs 在外周血(PB)和鼻窦组织中的作用。
从 16 例 CRS 患者和 5 例对照者中获取鼻窦组织,从另外 16 例 CRS 患者和总共 20 例对照者中获取 PB。对鼻窦组织进行免疫组织化学分析(CD3(+)、CD4(+)、CD8(+)和 Treg [CD4(+)-FoxP3(+)和 CD25(+)-FoxP3(+)])。通过流式细胞术分析 PB Tregs(CD4(+)-CD25(+)-FoxP3(+)细胞)的百分比。通过酶联免疫吸附试验(ELISA)测定 PB 单核细胞(PBMC)自发和植物血球凝集素(PHA)诱导释放的细胞因子(IL-6、IL-4、IL-10、干扰素 γ、转化生长因子[TGF]β1 和 TNF-α)。
与健康对照者相比,CRS 患者的 PB 流式细胞术分析显示 Tregs 百分比较低(p = 0.0003)。尽管 CRS 伴鼻息肉(CRSwNP)和不伴鼻息肉(CRSsNP)患者的 PB Treg 计数无差异,但对鼻窦组织进行的免疫组化分析显示,CRSwNP 患者的 Treg 比例高于 CRSsNP(p < 0.05)。此外,我们未能从对照蝶窦组织中检测到任何 Tregs。与对照者相比,CRS 患者的 PBMCs 中调节性细胞因子(IL-10 和 TGF-β1)水平较低,促炎细胞因子(TNF-α和 IL-6)水平较高(p < 0.05)。
我们的研究结果表明,与正常对照者相比,CRS 患者的 PB Tregs 百分比较低。CRS 患者的 PBMCs 表现出更强的促炎和较弱的调节表型。