高T2型及低T2型哮喘气道免疫功能紊乱的转录组测定
2018/11/14
摘要
背景：在许多哮喘患者中，2型（T2）炎症导致气道功能障碍，但是对维持这种炎症的气道免疫细胞类型和网络的全面了解尚不清楚。此外，尚不清楚哮喘患者是否存在T2炎症的气道免疫系统缺陷。
目的：探讨高T2型哮喘患者维持高T2气道炎症水平的基因网络和低T2型哮喘的基因网络。
方法：对84例哮喘患者和27例健康人痰液细胞转录组表达数据进行网络分析，确定以哮喘亚群为基础的免疫细胞类型富集网络。
结果：痰T2基因表达的特征是免疫细胞网络衍生自多种先天免疫细胞，包括嗜酸性粒细胞、肥大细胞/嗜碱性粒细胞和炎性树突状细胞。将具有这种免疫细胞网络的受试者聚类分层分为高T2型和低T2型，但同样显示高T2型受试者中有T2免疫细胞网络均高表达的亚组。这些“T2超高个体”的临床特征是年龄较大和更严重的气流阻塞，病理特征是第二级T2型网络，起源于向T2倾斜的CD11b+/CD103-/IRF4+经典树突状细胞。低T2型哮喘患者与健康对照组通过低表达细胞毒性CD8+T细胞网络进行鉴别，该细胞毒性CD8+T细胞网络与体重指数和血浆IL-6水平均呈负相关。
结论：持续存在的T2型气道炎症是由先天和适应性免疫基因表达网络组成的复杂结构，在不同哮喘患者中不同，尽管接受了类固醇激素的治疗，这些基因表达网络仍然存在。低T2型哮喘在细胞毒性T细胞活性方面表现出的气道缺陷与肥胖驱动的炎症相关。
A Transcriptomic Method to Determine Airway Immune Dysfunction in T2-High and T2-Low Asthma.
Peters MC, Ringel L, Dyjack N, Herrin R, Woodruff PG, Rios C, O'Connor B, Fahy JV, Seibold MA.
Abstract
BACKGROUND: Type-2 (T2) inflammation drives airway dysfunction in many asthma patients, yet a comprehensive understanding of the airway immune cell types and networks that sustain this inflammation is unknown. Moreover, it is unclear whether defects in the airway immune system exist in asthmatics without T2 inflammation.
OBJECTIVE: To determine the gene networks that sustain T2 airway inflammation in T2-high asthma and to explore the gene networks that characterize T2-low asthma.
METHODS: Network analysis of sputum cell transcriptome expression data from 84 asthmatics and 27 healthy controls was used to identify immune cell type-enriched networks that underlie asthma subgroups.
RESULTS: Sputum T2 gene expression was characterized by an immune cell network derived from multiple innate immune cells including, eosinophils, mast cell/basophils, and inflammatory dendritic cells. Clustering of subjects with this network stratified subjects into T2-high and T2-low, but also revealed a subgroup of T2-high subjects with uniformly higher expression of the T2 network. These "T2-ultra high subjects" were characterized clinically by older age and more severe airflow obstruction and pathologically by a second T2 network derived from T2-skewed, CD11b+/CD103-/IRF4+ classical dendritic cells. T2-low asthmatics were differentiated from healthy controls by lower expression of a cytotoxic CD8+ T cell network, which was negatively correlated with both body mass index and plasma IL-6 levels.
CONCLUSIONS: Persistent airway T2 inflammation is a complex construct of innate and adaptive immunity gene expression networks, which are variable across asthmatics and persist despite to steroid treatment. T2-low asthmatics exhibit an airway deficiency in cytotoxic T cell activity associated with obesity-driven inflammation.
背景：在许多哮喘患者中，2型（T2）炎症导致气道功能障碍，但是对维持这种炎症的气道免疫细胞类型和网络的全面了解尚不清楚。此外，尚不清楚哮喘患者是否存在T2炎症的气道免疫系统缺陷。
目的：探讨高T2型哮喘患者维持高T2气道炎症水平的基因网络和低T2型哮喘的基因网络。
方法：对84例哮喘患者和27例健康人痰液细胞转录组表达数据进行网络分析，确定以哮喘亚群为基础的免疫细胞类型富集网络。
结果：痰T2基因表达的特征是免疫细胞网络衍生自多种先天免疫细胞，包括嗜酸性粒细胞、肥大细胞/嗜碱性粒细胞和炎性树突状细胞。将具有这种免疫细胞网络的受试者聚类分层分为高T2型和低T2型，但同样显示高T2型受试者中有T2免疫细胞网络均高表达的亚组。这些“T2超高个体”的临床特征是年龄较大和更严重的气流阻塞，病理特征是第二级T2型网络，起源于向T2倾斜的CD11b+/CD103-/IRF4+经典树突状细胞。低T2型哮喘患者与健康对照组通过低表达细胞毒性CD8+T细胞网络进行鉴别，该细胞毒性CD8+T细胞网络与体重指数和血浆IL-6水平均呈负相关。
结论：持续存在的T2型气道炎症是由先天和适应性免疫基因表达网络组成的复杂结构，在不同哮喘患者中不同，尽管接受了类固醇激素的治疗，这些基因表达网络仍然存在。低T2型哮喘在细胞毒性T细胞活性方面表现出的气道缺陷与肥胖驱动的炎症相关。
(中日友好医院呼吸与危重症医学科 李红雯 摘译 林江涛 审校)
(Am J Respir Crit Care Med. 2018 Oct 29. doi: 10.1164/rccm.201807-1291OC.)
(Am J Respir Crit Care Med. 2018 Oct 29. doi: 10.1164/rccm.201807-1291OC.)
A Transcriptomic Method to Determine Airway Immune Dysfunction in T2-High and T2-Low Asthma.
Peters MC, Ringel L, Dyjack N, Herrin R, Woodruff PG, Rios C, O'Connor B, Fahy JV, Seibold MA.
Abstract
BACKGROUND: Type-2 (T2) inflammation drives airway dysfunction in many asthma patients, yet a comprehensive understanding of the airway immune cell types and networks that sustain this inflammation is unknown. Moreover, it is unclear whether defects in the airway immune system exist in asthmatics without T2 inflammation.
OBJECTIVE: To determine the gene networks that sustain T2 airway inflammation in T2-high asthma and to explore the gene networks that characterize T2-low asthma.
METHODS: Network analysis of sputum cell transcriptome expression data from 84 asthmatics and 27 healthy controls was used to identify immune cell type-enriched networks that underlie asthma subgroups.
RESULTS: Sputum T2 gene expression was characterized by an immune cell network derived from multiple innate immune cells including, eosinophils, mast cell/basophils, and inflammatory dendritic cells. Clustering of subjects with this network stratified subjects into T2-high and T2-low, but also revealed a subgroup of T2-high subjects with uniformly higher expression of the T2 network. These "T2-ultra high subjects" were characterized clinically by older age and more severe airflow obstruction and pathologically by a second T2 network derived from T2-skewed, CD11b+/CD103-/IRF4+ classical dendritic cells. T2-low asthmatics were differentiated from healthy controls by lower expression of a cytotoxic CD8+ T cell network, which was negatively correlated with both body mass index and plasma IL-6 levels.
CONCLUSIONS: Persistent airway T2 inflammation is a complex construct of innate and adaptive immunity gene expression networks, which are variable across asthmatics and persist despite to steroid treatment. T2-low asthmatics exhibit an airway deficiency in cytotoxic T cell activity associated with obesity-driven inflammation.
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上皮SERPINB10是哮喘气道嗜酸性粒细胞增多的新标志物，增加气道过敏性炎症
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内皮细胞与过敏原先天反应和变应性哮喘发生
