Rhinology and Allergy, Nippon Medical School, Tokyo, Japan.
Allergy Asthma Immunol Res. 2012 Jan;4(1):24-30. doi: 10.4168/aair.2012.4.1.24. Epub 2011 Nov 9.
The pathogenesis of nasal polyposis (NP) is unclear. Eosinophils and mast cells are considered to play important roles in this process. In addition, the levels of Th2-type cells are increased, irrespective of the atopic status of the patient with NP. In this context, we and others have shown high levels of thymus and activation-related chemokine/CCL17, macrophage-derived chemokine, eotaxin, and RANTES in patients with NP. Forkhead box P3 (FOXP3) plays a key role in CD4+CD25+ regulatory T-cell function and represents a specific marker for regulatory T cells (Tregs). Decreased expression of FOXP3 has been reported in allergic diseases. The present study was designed to evaluate the presence and potential roles of Tregs, defined by the expression of FOXP3 protein, in NP.
Using immunohistochemistry, we estimated the numbers of FOXP3+ cells in the epithelium and lamina propria of the NPs of 17 patients with chronic rhinosinusitis with NP and the nasal mucosa of 15 patients with allergic rhinitis (AR). The number of FOXP3+ cells in NPs was compared with that in the nasal mucosa of patients with AR, and the numbers of FOXP3+ cells in atopic and non-atopic NP were also compared.
The number of FOXP3+ cells in the lamina propria of patients with NP was significantly lower than that in the nasal mucosa of the AR patients (2.79 vs. 5.99, P=0.008). There was no statistically significant difference noted for the numbers of FOXP3+ cells between the epithelium of the NP and the nasal mucosa (3.60 vs. 2.39, P=0.180). Furthermore, the numbers of CD4+FOXP3+ cells were lower in NPs than in the allergic nasal mucosa. There was no difference in the number of FOXP3+ cells between the atopic and non-atopic NP patients.
Fewer Tregs (i.e., decreased FOXP3 expression) are found in NPs than in the nasal mucosa of AR patients. As the severity of eosinophilic, Th2-type inflammation and the levels of inflammatory mediators are much higher in NPs than in the nasal mucosa of AR patients, an inverse co-relationship may exist between these parameters and the number of Tregs. The deficiency of Tregs in NP may account for the more pronounced Th2-type inflammation seen in these patients.
鼻息肉(NP)的发病机制尚不清楚。嗜酸性粒细胞和肥大细胞被认为在此过程中起重要作用。此外,无论 NP 患者是否存在特应性,Th2 型细胞的水平均升高。在这种情况下,我们和其他人已经在 NP 患者中发现高水平的胸腺激活相关趋化因子/CCL17、巨噬细胞衍生趋化因子、嗜酸性粒细胞趋化因子和 RANTES。叉头框 P3(FOXP3)在 CD4+CD25+调节性 T 细胞功能中起关键作用,是调节性 T 细胞(Treg)的特异性标志物。在过敏疾病中已报道 FOXP3 的表达减少。本研究旨在评估通过 FOXP3 蛋白表达定义的 Treg(调节性 T 细胞)在 NP 中的存在和潜在作用。
使用免疫组织化学方法,我们估计了 17 例慢性鼻-鼻窦炎伴 NP 患者的 NP 上皮和固有层以及 15 例变应性鼻炎(AR)患者的鼻黏膜中 FOXP3+细胞的数量。将 NP 中的 FOXP3+细胞数量与 AR 患者的鼻黏膜进行比较,并比较了特应性和非特应性 NP 中的 FOXP3+细胞数量。
NP 患者固有层中的 FOXP3+细胞数量明显低于 AR 患者的鼻黏膜(2.79 对 5.99,P=0.008)。NP 上皮中的 FOXP3+细胞数量与鼻黏膜之间无统计学差异(3.60 对 2.39,P=0.180)。此外,NP 中的 CD4+FOXP3+细胞数量低于变应性鼻黏膜。特应性和非特应性 NP 患者的 FOXP3+细胞数量无差异。
与 AR 患者的鼻黏膜相比,NP 中 Treg(即 FOXP3 表达减少)较少。由于 NP 中的嗜酸性粒细胞、Th2 型炎症的严重程度以及炎症介质的水平均远高于 AR 患者的鼻黏膜,这些参数与 Treg 数量之间可能存在反比关系。NP 中 Treg 的缺乏可能是这些患者中更明显的 Th2 型炎症的原因。