Title :

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

Author(s) :

Dill-McFarland, Kimberly A [Auteur]
University of Washington [Seattle]
Altman, Matthew C [Auteur]
University of Washington [Seattle]
Esnault, Stephane [Auteur]
University of Wisconsin-Madison
Jarjour, Nizar N [Auteur]
University of Wisconsin-Madison
Busse, William W [Auteur]
University of Wisconsin-Madison
Rosenkranz, Melissa A [Auteur]
University of Wisconsin-Madison

Journal title :

The journal of allergy and clinical immunology

Abbreviated title :

J Allergy Clin Immunol

Publication date :

2023-09-19

ISSN :

1097-6825

English keyword(s) :

Asthma
IL-17
T(H)17
depression
eosinophils
fMRI
gene expression network analysis
salience network

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

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 ...
Show more >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.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Autres travaux scientifiques

Submission date :

2023-10-22T06:18:45Z
2023-12-06T10:43:33Z