ILC2细胞参与IL-2联合IL-18诱导小鼠间质性肺病发病的研究

ILC2 involved in the pathogenesis of pulmonary interstitial disease mice model induced by the combination of IL-2 and IL-18

将18只雌性6周龄B6小鼠随机分为试验组和对照组,经腹腔注射不同剂量白介素-2 (IL-2)及IL-18,观察肺组织病理改变及双调蛋白(AREG)免疫组织化学,酶联免疫吸附法(ELISA)检测血清及肺泡灌洗液(BALF)中相关细胞因子,流式细胞仪检测肺脏、脾脏、肠系膜淋巴结(MLN)中2型固有淋巴细胞(ILC2)百分比,探讨小鼠间质性肺病(ILD)模型中ILC2及相关细胞因子变化情况。结果表明:试验组相比对照组小鼠肺部病理呈典型ILD样改变;试验组血清中AREG、IFN-γ和IL-17的表达均显著高于对照组;试验组肺脏、脾脏、MLN中ILC2百分比均显著高于对照组;肺脏免疫组织化学显示AREG的表达明显增多。这一研究提示联合注射一定剂量的IL-2和IL-18可导致小鼠ILD样病理变化, ILC2可能参与该动物模型的发病过程。

A total of 18 female mice at 6-weeks of age were randomized,intraperitoneally injected with different doses of IL-2 and IL-18.The pathological changes of lung tissue and immunochemistry of amphiregulin(AREG)were observed.The levels of innate lymphoid cell type 2(ILC2)related cytokines in blood and alveolar lavage fluid(BALF)were detected by enzyme-linked immunosorbent assay(ELISA).The percentage of ILC2 in lung,spleen and mesenteric lymph node(MLN)were analyzed by flow cytometry.ILC2 related cytokines in interstitial lung disease(ILD)mice model were investigated.The results revealed that compared with the control group,the lung pathology of the experimental group showed typical ILD-like changes.The levels of AREG,IFN-γand IL-17 in the serum of the experimental group were significantly higher than those in the control group.The proportion of ILC2 in lung,spleen and MLN was significantly increased in the experimental group.The expression of AREG in lung was significantly increased in experimental group.Our data suggest that the combination of IL-2 and IL-8 can induce the pathological changes of ILD in mice.ILC2 may be involved in the pathogenesis of ILD mice model.