St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia; Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, NSW, Australia.
Clin Exp Allergy. 2015 Feb;45(2):394-403. doi: 10.1111/cea.12462.
Chronic rhinosinusitis (CRS) is a heterogeneous disease with an uncertain pathogenesis. Group 2 innate lymphoid cells (ILC2s) represent a recently discovered cell population which has been implicated in driving Th2 inflammation in CRS; however, their relationship with clinical disease characteristics has yet to be investigated.
The aim of this study was to identify ILC2s in sinus mucosa in patients with CRS and controls and compare ILC2s across characteristics of disease.
A cross-sectional study of patients with CRS undergoing endoscopic sinus surgery was conducted. Sinus mucosal biopsies were obtained during surgery and control tissue from patients undergoing pituitary tumour resection through transphenoidal approach. ILC2s were identified as CD45(+) Lin(-) CD127(+) CD4(-) CD8(-) CRTH2(CD294)(+) CD161(+) cells in single cell suspensions through flow cytometry. ILC2 frequencies, measured as a percentage of CD45(+) cells, were compared across CRS phenotype, endotype, inflammatory CRS subtype and other disease characteristics including blood eosinophils, serum IgE, asthma status and nasal symptom score.
35 patients (40% female, age 48 ± 17 years) including 13 with eosinophilic CRS (eCRS), 13 with non-eCRS and 9 controls were recruited. ILC2 frequencies were associated with the presence of nasal polyps (P = 0.002) as well as high tissue eosinophilia (P = 0.004) and eosinophil-dominant CRS (P = 0.001) (Mann-Whitney U). They were also associated with increased blood eosinophilia (P = 0.005). There were no significant associations found between ILC2s and serum total IgE and allergic disease. In the CRS with nasal polyps (CRSwNP) population, ILC2s were increased in patients with co-existing asthma (P = 0.03). ILC2s were also correlated with worsening nasal symptom score in CRS (P = 0.04).
As ILC2s are elevated in patients with CRSwNP, they may drive nasal polyp formation in CRS. ILC2s are also linked with high tissue and blood eosinophilia and have a potential role in the activation and survival of eosinophils during the Th2 immune response. The association of innate lymphoid cells in CRS provides insights into its pathogenesis.
慢性鼻-鼻窦炎（CRS）是一种具有不确定发病机制的异质性疾病。2 型固有淋巴细胞（ILC2）是最近发现的一种细胞群，它被认为在 CRS 中驱动 Th2 炎症；然而，它们与临床疾病特征的关系尚未被研究。
本研究的目的是鉴定 CRS 患者和对照者鼻窦黏膜中的 ILC2，并比较 ILC2 在疾病特征中的差异。
对接受内镜鼻窦手术的 CRS 患者进行了一项横断面研究。在手术中获得鼻窦黏膜活检，并从接受经蝶窦入路垂体瘤切除术的患者中获得对照组织。通过流式细胞术，在单细胞悬液中，将 ILC2 鉴定为 CD45（+）Lin（-）CD127（+）CD4（-）CD8（-）CRTH2（CD294）（+）CD161（+）细胞。通过流式细胞术，将 ILC2 频率（以 CD45（+）细胞的百分比表示）与 CRS 表型、内型、炎症性 CRS 亚型以及其他疾病特征（包括血嗜酸性粒细胞、血清 IgE、哮喘状态和鼻症状评分）进行比较。
共招募了 35 名患者（40%为女性，年龄 48±17 岁），包括 13 名嗜酸粒细胞性 CRS（eCRS）患者、13 名非嗜酸粒细胞性 CRS 患者和 9 名对照者。ILC2 频率与鼻息肉的存在（P=0.002）、组织高嗜酸性粒细胞（P=0.004）和嗜酸性粒细胞占主导的 CRS（P=0.001）（Mann-Whitney U）相关。它们还与血嗜酸性粒细胞增多（P=0.005）相关。在 CRS 患者中，ILC2 与血清总 IgE 和过敏性疾病之间无显著相关性。在伴有鼻息肉的 CRSwNP 患者中，合并哮喘的患者 ILC2 增加（P=0.03）。在 CRS 中，ILC2 与鼻症状评分恶化相关（P=0.04）。
由于 ILC2 在 CRSwNP 患者中升高，因此它们可能在 CRS 中驱动鼻息肉形成。ILC2 还与高组织和血嗜酸性粒细胞相关，在 Th2 免疫反应中，它们在嗜酸性粒细胞的激活和存活中可能发挥作用。CRS 中固有淋巴细胞的相关性提供了对其发病机制的深入了解。
