Molecular pathways underlying lung-brain axis signaling in asthma: relevance for psychopathology and neuroinflammation. - Université de Lille Accéder directement au contenu
Article Dans Une Revue The journal of allergy and clinical immunology Année : 2023

Molecular pathways underlying lung-brain axis signaling in asthma: relevance for psychopathology and neuroinflammation.

Résumé

Accumulating evidence indicates that asthma has systemic effects and impacts 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 to brain communication during airway inflammation in asthma. In twenty-three adults with mild asthma, segmental bronchial provocation with allergen (SBP-Ag) was used to provoke airway inflammation and retrieve bronchoalveolar lavage (BAL) 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 48h post-SBP-Ag. Cell deconvolution and gene co-expression network analysis identified 11 cell-associated gene modules that changed in response to SBP-Ag. SBP-Ag increased BAL eosinophils and expression of an eosinophil-associated module enriched for genes related to Th17-type inflammation (e.g., IL17A), as well as cell proliferation in lung and brain (e.g., NOTCH1, VEGFA, LIF). Increased expression of genes in this module, as well as several Th17-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, Th17-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.
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Dates et versions

hal-04249179 , version 1 (19-10-2023)

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Citer

Kimberly A Dill-Mcfarland, Matthew C Altman, Stéphane Esnault, Nizar N Jarjour, William W Busse, et al.. Molecular pathways underlying lung-brain axis signaling in asthma: relevance for psychopathology and neuroinflammation.. The journal of allergy and clinical immunology, 2023, The journal of allergy and clinical immunology, ⟨10.1016/j.jaci.2023.07.025⟩. ⟨hal-04249179⟩

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