Department of Otorhinolaryngology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Department of Clinical Immunology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Front Immunol. 2018 Sep 19;9:2121. doi: 10.3389/fimmu.2018.02121. eCollection 2018.
Chronic rhinosinusitis (CRS) is a common chronic inflammatory disease of the upper airways involving nasal cavity and sinus. Deriving both from its clinical complexity with protean clinical manifestations as well its pathogenetic heterogeneity, the molecular mechanisms contributing to the pathogenesis of CRS remain unclear, and attract a wide interest in the field. Current evidences indicate that IL-17A is highly expressed in chronic rhinosinusitis with nasal polyps (CRSwNP). However, its pathogenetic role in regulation of tissue remodeling of CRSwNP remains unknown. The present study aimed to investigate the cellular origins and functions of IL-17A cytokine in CRSwNP, and further determined whether IL-17A could affect the expression of metalloproteinases (MMPs), the remodeling factors of CRSwNP. The results showed that the expression of IL-17A was upregulated in nasal tissues of patients with CRSwNP compared to those with chronic rhinosinusitis without nasal polyps (CRSsNP) and controls. CD8 cytotoxic T lymphocytes (Tc) were major IL-17A producers in nasal tissues of CRSwNP. Interleukin (IL)-17-producing CD8 T cells (Tc17) was significantly higher in nasal tissues of CRSwNP than CRSsNP and controls. Nonetheless, no difference was observed among the IL-17A in peripheral blood lymphocytes of these three groups. Moreover, in the same patients, IL-17A expression was negligible in lymphocytes of peripheral blood when compared with nasal tissues. Increased gene and protein expression of MMP-7 and MMP-9 in patients with CRSwNP compared with controls were observed. In CRSwNP samples, IL-17A receptor (IL-17AR) co-localized with MMP-9 and they were mainly expressed in the epithelial cells. MMP-9 expression was up-regulated both in Primary human nasal epithelial cells (PHNECs) and a nasal epithelial cell line (RPMI 2650) by IL-17A treatment, and diminished by anti-IL-17AR treatment. Furthermore, IL-17A promoted the expression of MMP-9 by activating the NF-κB signal pathway. Thus, our results have revealed a crucial role of IL-17A and Tc cells on pathogenesis and tissue remodeling of CRSwNP.
慢性鼻-鼻窦炎(CRS)是一种常见的上呼吸道慢性炎症性疾病,涉及鼻腔和鼻窦。由于其临床表现复杂多样,发病机制也存在异质性,导致目前仍不清楚导致 CRS 发病的分子机制,并引起了该领域的广泛关注。目前的证据表明,白细胞介素-17A(IL-17A)在伴有鼻息肉的慢性鼻-鼻窦炎(CRSwNP)中高度表达。然而,其在调节 CRSwNP 组织重塑中的发病机制作用尚不清楚。本研究旨在探讨白细胞介素-17A(IL-17A)在 CRSwNP 中的细胞起源和功能,并进一步确定 IL-17A 是否可以影响 CRSwNP 重塑因子金属蛋白酶(MMPs)的表达。结果表明,与慢性鼻-鼻窦炎不伴鼻息肉(CRSsNP)和对照组相比,CRSwNP 患者的鼻组织中 IL-17A 的表达上调。CD8 细胞毒性 T 淋巴细胞(Tc)是鼻组织中 IL-17A 的主要产生细胞。CRSwNP 患者鼻组织中产生白细胞介素(IL)-17A 的 CD8 T 细胞(Tc17)明显高于 CRSsNP 和对照组。然而,三组患者外周血淋巴细胞中的 IL-17A 无差异。此外,在同一患者中,与鼻组织相比,外周血淋巴细胞中的 IL-17A 表达可忽略不计。与对照组相比,CRSwNP 患者 MMP-7 和 MMP-9 的基因和蛋白表达增加。在 CRSwNP 样本中,IL-17A 受体(IL-17AR)与 MMP-9 共定位,主要表达在上皮细胞中。IL-17A 处理可上调原代人鼻上皮细胞(PHNECs)和鼻上皮细胞系(RPMI 2650)中 MMP-9 的表达,并通过抗 IL-17AR 处理减少 MMP-9 的表达。此外,IL-17A 通过激活 NF-κB 信号通路促进 MMP-9 的表达。因此,我们的研究结果揭示了 IL-17A 和 Tc 细胞在 CRSwNP 的发病机制和组织重塑中的关键作用。
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