Division of Allergy and Infectious Diseases, University of Washington, Seattle, Wash.
Division of Allergy and Infectious Diseases, University of Washington, Seattle, Wash; Systems Immunology Program, Benaroya Research Institute, Seattle, Wash.
J Allergy Clin Immunol. 2024 Jan;153(1):111-121. doi: 10.1016/j.jaci.2023.07.025. Epub 2023 Sep 19.
Accumulating evidence indicates that asthma has systemic effects and affects brain function. Although airway inflammation is proposed to initiate afferent communications with the brain, the signaling pathways have not been established.
We sought to identify the cellular and molecular pathways involved in afferent lung-brain communication during airway inflammation in asthma.
In 23 adults with mild asthma, segmental bronchial provocation with allergen (SBP-Ag) was used to provoke airway inflammation and retrieve bronchoalveolar lavage fluid for targeted protein analysis and RNA sequencing to determine gene expression profiles. Neural responses to emotional cues in nodes of the salience network were assessed with functional magnetic resonance imaging at baseline and 48 hours after SBP-Ag.
Cell deconvolution and gene coexpression network analysis identified 11 cell-associated gene modules that changed in response to SBP-Ag. SBP-Ag increased bronchoalveolar lavage eosinophils and expression of an eosinophil-associated module enriched for genes related to T17-type inflammation (eg, IL17A), as well as cell proliferation in lung and brain (eg, NOTCH1, VEGFA, and LIF). Increased expression of genes in this module, as well as several T17-type inflammation-related proteins, was associated with an increase from baseline in salience network reactivity.
Our results identify a specific inflammatory pathway linking asthma-related airway inflammation and emotion-related neural function. Systemically, T17-type inflammation has been implicated in both depression and neuroinflammation, with impacts on long-term brain health. Thus, our data emphasize that inflammation in the lung in asthma may have profound effects outside of the lung that may be targetable with novel therapeutic approaches.
越来越多的证据表明哮喘具有全身性影响，并影响大脑功能。虽然气道炎症被认为引发了与大脑的传入通讯，但信号通路尚未确定。
我们旨在确定哮喘气道炎症期间参与肺-脑传入通讯的细胞和分子途径。
在 23 名轻度哮喘成人中，使用过敏原分段支气管激发（SBP-Ag）来激发气道炎症，并取回支气管肺泡灌洗液进行靶向蛋白分析和 RNA 测序，以确定基因表达谱。在 SBP-Ag 前后 48 小时，使用功能磁共振成像评估情感线索在显着性网络节点中的神经反应。
细胞去卷积和基因共表达网络分析确定了 11 个与 SBP-Ag 反应相关的细胞相关基因模块。SBP-Ag 增加了支气管肺泡灌洗液中的嗜酸性粒细胞和富含与 T17 型炎症相关基因的嗜酸性粒细胞相关模块的表达（例如，IL17A），以及肺和脑中的细胞增殖（例如，NOTCH1、VEGFA 和 LIF）。该模块中基因的表达增加，以及几种 T17 型炎症相关蛋白的表达增加，与显着性网络反应从基线开始增加相关。
我们的结果确定了一种特定的炎症途径，将哮喘相关的气道炎症与情绪相关的神经功能联系起来。在全身范围内，T17 型炎症与抑郁和神经炎症都有关联，对长期大脑健康有影响。因此，我们的数据强调，哮喘中的肺部炎症可能对肺部以外的组织产生深远影响，可能成为新的治疗方法的靶点。
