Department of Otolaryngology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Pediatr Allergy Immunol. 2022 Feb;33(2):e13717. doi: 10.1111/pai.13717.
Eosinophils play critical roles in the development of allergic rhinitis (AR) by releasing toxic substance. Interleukin-35 (IL-35), a newly identified anti-inflammatory cytokine, had potent inhibitive role for eosinophil infiltration in allergic disease. However, the direct effect of IL-35 on eosinophil was not clear.
Twenty AR children and sixteen controls were recruited. The correlation between IL-35 protein expression and blood eosinophil counts and activation was analyzed. The effect of IL-35 on eosinophil apoptosis and adhesion was analyzed by flow cytometry. Transwell system was used for the migration assay. The eosinophil cationic protein (ECP) from supernatant of eosinophils after IL-35 stimulation was detected by enzyme-linked immunosorbent assay kits.
The IL-35 protein levels were negatively correlated with eosinophil counts (p < .01) and ECP concentration (p < .01) in AR children. IL-35 promotes apoptosis and inhibits adhesion, migration, and activation of eosinophils. Moreover, the mRNA expression of IL-12 receptor β2 and glycoprotein 130 were significantly enhanced by eosinophils after IL-35 stimulation. The apoptosis induced by IL-35 was mediated by phosphoinositide 3-kinase (PI3K) pathway. IL-35 inhibits adhesion of eosinophils through extracellular regulated protein kinases (ERK) and PI3K pathways. The eosinophil chemotaxis and activation affected by IL-35 were mediated by PI3K and p38 mitogen-activated protein kinase (MAPK) pathways.
Our results confirmed that IL-35 played inhibitive roles in apoptosis, adhesion, migration, and activation of eosinophils in AR, implying that IL-35 may be used as treatment target in future.
嗜酸性粒细胞通过释放毒性物质在过敏性鼻炎（AR）的发展中起关键作用。白细胞介素-35（IL-35）是一种新发现的抗炎细胞因子，对过敏性疾病中的嗜酸性粒细胞浸润具有很强的抑制作用。然而，IL-35 对嗜酸性粒细胞的直接作用尚不清楚。
招募了 20 名 AR 儿童和 16 名对照者。分析了 IL-35 蛋白表达与血嗜酸性粒细胞计数和激活的相关性。通过流式细胞术分析 IL-35 对嗜酸性粒细胞凋亡和黏附的影响。用 Transwell 系统进行迁移实验。用酶联免疫吸附试验试剂盒检测 IL-35 刺激后嗜酸性粒细胞上清液中的嗜酸性粒细胞阳离子蛋白（ECP）。
AR 儿童的 IL-35 蛋白水平与嗜酸性粒细胞计数（p<0.01）和 ECP 浓度（p<0.01）呈负相关。IL-35 促进嗜酸性粒细胞凋亡，抑制黏附、迁移和激活。此外，IL-35 刺激后嗜酸性粒细胞的白细胞介素 12 受体 β2 和糖蛋白 130 的 mRNA 表达明显增强。IL-35 诱导的凋亡是通过磷酸肌醇 3-激酶（PI3K）途径介导的。IL-35 通过细胞外调节蛋白激酶（ERK）和 PI3K 途径抑制嗜酸性粒细胞的黏附。IL-35 影响嗜酸性粒细胞的趋化和激活是通过 PI3K 和 p38 丝裂原激活蛋白激酶（MAPK）途径介导的。
我们的结果证实，IL-35 在 AR 中抑制嗜酸性粒细胞的凋亡、黏附、迁移和激活，这意味着 IL-35 可能成为未来的治疗靶点。
