Zeng Yinhui, Zeng Qingxiang, Wen Yueqiang, Li Jinyuan, Xiao Haiqing, Yang Chao, Luo Renzhong, Liu Wenlong
Department of Otolaryngology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, China.
Department of Nephrology, the Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
J Allergy Clin Immunol Glob. 2024 Jan 17;3(2):100212. doi: 10.1016/j.jacig.2024.100212. eCollection 2024 May.
Group 2 innate lymphoid cells (ILC2s) have been found to take part in type 2 inflammation by secreting T2 cytokines. Apolipoprotein A-I (Apo-AI), a major structural and functional protein of high-density lipoproteins, has anti-inflammatory effects on neutrophils, monocytes, macrophages, and eosinophils. However, its effects on ILC2s are not well characterized.
We aimed to investigate the effect of Apo-AI on the proliferation and function of ILC2s as well as its possible mechanism.
The protein expression of Apo-AI and the percentage of ILC2s in peripheral blood between 20 allergic rhinitis patients and 20 controls were detected by ELISA and flow cytometry. The effect of Apo-AI and miR-155 on ILC2 proliferation and function was detected by tritiated thymidine incorporation and ELISA. Anima models were adopted to verify the effect of Apo-AI .
Elevated expression of Apo-AI was observed in allergic rhinitis patients. Apo-AI promotes expression by ILC2s, which can be inhibited by anti-Apo-AI. Apo-AI decreased ILC2 proliferation and the microRNA levels of GATA3 and RORα from ILC2s. The miR-155 overexpression promoted the upregulation of GATA3 and type II cytokines from ILC2s, while the addition of Apo-AI or miR-155 inhibitor significantly inhibited expression of GATA3 and type II cytokines by ILC2s. Apo-AI mice showed as enhanced allergen-induced airway inflammation. The miR-155 inhibitor can reverse the enhanced allergen-induced airway inflammation in Apo-AI mice, while miR-155 mimics can reverse the decreased allergen-induced airway inflammation in Apo-AI-treated mice.
Apo-AI suppressed the proliferation and function of ILC2s through miR-155 in allergic rhinitis. Our data provide new insights into the mechanism of allergen-induced airway inflammation.
已发现2型固有淋巴细胞（ILC2s）通过分泌2型细胞因子参与2型炎症反应。载脂蛋白A-I（Apo-AI）是高密度脂蛋白的主要结构和功能蛋白，对中性粒细胞、单核细胞、巨噬细胞和嗜酸性粒细胞具有抗炎作用。然而，其对ILC2s的影响尚未完全明确。
我们旨在研究Apo-AI对ILC2s增殖和功能的影响及其可能机制。
采用酶联免疫吸附测定（ELISA）和流式细胞术检测20例变应性鼻炎患者和20例对照者外周血中Apo-AI的蛋白表达及ILC2s的百分比。采用氚标记胸腺嘧啶核苷掺入法和ELISA检测Apo-AI和微小RNA-155（miR-155）对ILC2s增殖和功能的影响。采用动物模型验证Apo-AI的作用。
变应性鼻炎患者中观察到Apo-AI表达升高。Apo-AI促进ILC2s的表达，抗Apo-AI可抑制该作用。Apo-AI降低ILC2s的增殖以及ILC2s中GATA3和RORα的微小RNA水平。miR-155过表达促进ILC2s中GATA3和2型细胞因子的上调，而添加Apo-AI或miR-155抑制剂可显著抑制ILC2s对GATA3和2型细胞因子的表达。Apo-AI小鼠表现为变应原诱导的气道炎症增强。miR-155抑制剂可逆转Apo-AI小鼠中变应原诱导的气道炎症增强，而miR-155模拟物可逆转Apo-AI处理小鼠中变应原诱导的气道炎症减弱。
在变应性鼻炎中，Apo-AI通过miR-155抑制ILC2s的增殖和功能。我们的数据为变应原诱导的气道炎症机制提供了新的见解。
