哮喘气道的固有免疫串话：固有淋巴细胞调节肺巨噬细胞的极化
2019/06/28
摘要
背景：最近的研究强调了固有淋巴细胞（innate lymphoid cells，ILC）在哮喘发展中的作用。2型固有淋巴细胞（ILC2）在哮喘中的作用研究较深入，但其他亚型的固有淋巴细胞参与哮喘发展的作用仍不清楚。
目的：本研究旨在了解各种固有淋巴细胞在哮喘中的作用，尤其是对巨噬细胞极化的影响。
方法：纳入51名未接受激素治疗的哮喘患者和18名健康对照，采用流式细胞术分析他们诱导痰中的固有淋巴细胞和巨噬细胞的各个亚型。对肺泡巨噬细胞进行分类，并与固有淋巴细胞各亚型共培养，以确定固有淋巴细胞是否能调节巨噬细胞的极化。
结果：与健康对照组相比，除ILC2外，哮喘患者诱导痰中1型固有淋巴细胞（ILC1）和3型固有淋巴细胞（ILC3）数量都增加。诱导痰中巨噬细胞数量也较健康对照组增多。ILC2数量与M2巨噬细胞数量、ILC1/ILC3数量和M1巨噬细胞数量之间呈正相关。通过细胞因子分泌以及细胞-细胞接触的方式，ILC2与肺泡巨噬细胞共培养可诱导M2巨噬细胞相关基因的表达，而ILC1和ILC3与肺泡巨噬细胞共培养可诱导M1巨噬细胞相关基因的表达。根据炎症特征，嗜酸粒细胞性哮喘患者ILC2和M2巨噬细胞更多，非嗜酸粒细胞性哮喘患者M1巨噬细胞更多。
结论：固有淋巴细胞的不同亚型调节巨噬细胞的极化，从而形成哮喘的不同表型。
Innate immune crosstalk in asthmatic airways: Innate lymphoid cells coordinate polarization of lung macrophages
Jihyun Kim, BS, Yuna Chang, BS, Boram Bae, BS, Kyoung-Hee Sohn, MD, Sang-Heon Cho, MD, PhD, Doo Hyun Chung, MD, PhD, Hye Ryun Kang, MD, PhD, and Hye Young Kim, PhD
J Allergy Clin Immunol; 2019 May; 143(5):1769-1782.
Abstract
Background: 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.
Objective: This study aims to understand the role of various ILCs in patients with asthma, especially their effect on macrophage polarization.
Methods: 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.
Results: 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.
Conclusions: A different subset of ILCs regulates macrophage polarization, contributing to developing the distinct phenotype of asthma.
背景：最近的研究强调了固有淋巴细胞（innate lymphoid cells，ILC）在哮喘发展中的作用。2型固有淋巴细胞（ILC2）在哮喘中的作用研究较深入，但其他亚型的固有淋巴细胞参与哮喘发展的作用仍不清楚。
目的：本研究旨在了解各种固有淋巴细胞在哮喘中的作用，尤其是对巨噬细胞极化的影响。
方法：纳入51名未接受激素治疗的哮喘患者和18名健康对照，采用流式细胞术分析他们诱导痰中的固有淋巴细胞和巨噬细胞的各个亚型。对肺泡巨噬细胞进行分类，并与固有淋巴细胞各亚型共培养，以确定固有淋巴细胞是否能调节巨噬细胞的极化。
结果：与健康对照组相比，除ILC2外，哮喘患者诱导痰中1型固有淋巴细胞（ILC1）和3型固有淋巴细胞（ILC3）数量都增加。诱导痰中巨噬细胞数量也较健康对照组增多。ILC2数量与M2巨噬细胞数量、ILC1/ILC3数量和M1巨噬细胞数量之间呈正相关。通过细胞因子分泌以及细胞-细胞接触的方式，ILC2与肺泡巨噬细胞共培养可诱导M2巨噬细胞相关基因的表达，而ILC1和ILC3与肺泡巨噬细胞共培养可诱导M1巨噬细胞相关基因的表达。根据炎症特征，嗜酸粒细胞性哮喘患者ILC2和M2巨噬细胞更多，非嗜酸粒细胞性哮喘患者M1巨噬细胞更多。
结论：固有淋巴细胞的不同亚型调节巨噬细胞的极化，从而形成哮喘的不同表型。
(王霁1 张欣1,3 张红萍1 王刚2,3 四川大学华西医院中西医结合科呼吸病组 610041 摘译)
（J Allergy Clin Immunol; 2019 May; 143(5):1769-1782.）
（J Allergy Clin Immunol; 2019 May; 143(5):1769-1782.）
Innate immune crosstalk in asthmatic airways: Innate lymphoid cells coordinate polarization of lung macrophages
Jihyun Kim, BS, Yuna Chang, BS, Boram Bae, BS, Kyoung-Hee Sohn, MD, Sang-Heon Cho, MD, PhD, Doo Hyun Chung, MD, PhD, Hye Ryun Kang, MD, PhD, and Hye Young Kim, PhD
J Allergy Clin Immunol; 2019 May; 143(5):1769-1782.
Abstract
Background: 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.
Objective: This study aims to understand the role of various ILCs in patients with asthma, especially their effect on macrophage polarization.
Methods: 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.
Results: 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.
Conclusions: A different subset of ILCs regulates macrophage polarization, contributing to developing the distinct phenotype of asthma.
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不同哮喘表型痰柱状上皮细胞及其产物的失调
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探讨非侵入性Th2型炎症标志物在预测儿童和青少年严重哮喘恶化中的作用
