Laboratory of Mucosal Immunology in the Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, Korea.
J Allergy Clin Immunol. 2019 May;143(5):1769-1782.e11. doi: 10.1016/j.jaci.2018.10.040. Epub 2018 Nov 9.
Recent studies have emphasized the role of innate lymphoid cells (ILCs) in the development of asthma. The involvement of group 2 innate lymphoid cells (ILC2s) in asthma is well studied: however, the participation of other types of ILCs in the development of asthma remains unclear.
This study aims to understand the role of various ILCs in patients with asthma, especially their effect on macrophage polarization.
Each subset of ILCs and macrophages in induced sputum from 51 steroid-naive patients with asthma and 18 healthy donors was analyzed by using flow cytometry. Alveolar macrophages (AM) were sorted and cocultured with each subset of ILCs to determine whether the polarization of macrophages could be regulated by ILCs.
In addition to ILC2s, numbers of group 1 innate lymphoid cells (ILC1s) and group 3 innate lymphoid cells (ILC3s) were increased in induced sputum from asthmatic patients when compared with those in healthy control subjects. The dominance of macrophages in induced sputum was more prominent in asthmatic patients than in healthy control subjects. A positive correlation between numbers of ILC2s and numbers of M2 macrophages and those of ILC1s/ILC3s and M1 macrophages was observed. Coculture of ILC2s with AMs induced expression of M2 macrophage-related genes, whereas coculture of ILC1s and ILC3s with AMs induced expression of M1 macrophage-related genes through cytokine secretion, as well as cell-cell contact. According to the inflammatory signature, patients with eosinophilic asthma have more ILC2s and M2 macrophages, and those with noneosinophilic asthma have an M1 macrophage-dominant profile.
A different subset of ILCs regulates macrophage polarization, contributing to developing the distinct phenotype of asthma.
最近的研究强调了固有淋巴细胞（ILC）在哮喘发展中的作用。2 型固有淋巴细胞（ILC2）在哮喘中的作用已得到充分研究：然而，其他类型的 ILC 在哮喘发展中的参与仍不清楚。
本研究旨在了解各种 ILC 在哮喘患者中的作用，特别是它们对巨噬细胞极化的影响。
通过流式细胞术分析 51 例未经类固醇治疗的哮喘患者和 18 例健康供者诱导痰中的每个 ILC 亚群和巨噬细胞。分离肺泡巨噬细胞（AM）并与每个 ILC 亚群共培养，以确定 ILC 是否可以调节巨噬细胞的极化。
除 ILC2 外，哮喘患者诱导痰中的 ILC1 和 ILC3 数量也高于健康对照组。与健康对照组相比，哮喘患者诱导痰中巨噬细胞的优势更为明显。观察到 ILC2 数量与 M2 巨噬细胞数量以及 ILC1/ILC3 数量与 M1 巨噬细胞数量之间呈正相关。ILC2 与 AM 共培养诱导 M2 巨噬细胞相关基因的表达，而 ILC1 和 ILC3 与 AM 共培养通过细胞因子分泌和细胞间接触诱导 M1 巨噬细胞相关基因的表达。根据炎症特征，嗜酸性粒细胞性哮喘患者有更多的 ILC2 和 M2 巨噬细胞，而非嗜酸性粒细胞性哮喘患者则表现为 M1 巨噬细胞优势表型。
不同的 ILC 亚群调节巨噬细胞极化，有助于形成哮喘的独特表型。
