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Allergic Sensitization Driving Immune Phenotyping and Disease Severity in a Mouse Model of Asthma

PURPOSE: Asthma is a frequent chronic inflammatory bronchial disease affecting more than 300 million patients worldwide, 70% of whom are secondary to allergy. The diversity of asthmatic endotypes contributes to their complexity. The inter-relationship between allergen and other exposure and the airw...

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Autores principales: Dijoux, Eléonore, Klein, Martin, Misme-Aucouturier, Barbara, Cheminant, Marie-Aude, de Carvalho, Marion, Collin, Louise, Hassoun, Dorian, Delage, Erwan, Gourdel, Mathilde, Loirand, Gervaise, Sauzeau, Vincent, Magnan, Antoine, Bouchaud, Grégory
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Academy of Asthma, Allergy and Clinical Immunology; The Korean Academy of Pediatric Allergy and Respiratory Disease 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10079520/
https://www.ncbi.nlm.nih.gov/pubmed/37021509
http://dx.doi.org/10.4168/aair.2023.15.2.246
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author Dijoux, Eléonore
Klein, Martin
Misme-Aucouturier, Barbara
Cheminant, Marie-Aude
de Carvalho, Marion
Collin, Louise
Hassoun, Dorian
Delage, Erwan
Gourdel, Mathilde
Loirand, Gervaise
Sauzeau, Vincent
Magnan, Antoine
Bouchaud, Grégory
author_facet Dijoux, Eléonore
Klein, Martin
Misme-Aucouturier, Barbara
Cheminant, Marie-Aude
de Carvalho, Marion
Collin, Louise
Hassoun, Dorian
Delage, Erwan
Gourdel, Mathilde
Loirand, Gervaise
Sauzeau, Vincent
Magnan, Antoine
Bouchaud, Grégory
author_sort Dijoux, Eléonore
collection PubMed
description PURPOSE: Asthma is a frequent chronic inflammatory bronchial disease affecting more than 300 million patients worldwide, 70% of whom are secondary to allergy. The diversity of asthmatic endotypes contributes to their complexity. The inter-relationship between allergen and other exposure and the airway microbiome adds to the phenotypic diversity and defines the natural course of asthma. Here, we compared the mouse models of house dust mite (HDM)-induced allergic asthma. Allergic sensitization was performed via various routes and associated with outcomes. METHODS: Mice were sensitized with HDM via the oral, nasal or percutaneous routes. Lung function, barrier integrity, immune response and microbiota composition were analyzed. RESULTS: Severe impairment of respiratory function was observed in the mice sensitized by the nasal and cutaneous paths. It was associated with epithelial dysfunction characterized by an increased permeability secondary to junction protein disruption. Such sensitization paths induced a mixed eosinophilic and neutrophilic inflammatory response with high interleukin (IL)-17 airway secretion. In contrast, orally sensitized mice showed a mild impairment of respiratory function. Epithelial dysfunction was mild with increased mucus production, but preserved epithelial junctions. Regarding lung microbiota, sensitization provoked a significant loss of diversity. At the genus level, Cutibacterium, Acinetobacter, Streptococcus and Lactobacillus were found to be modulated according to the sensitization pathway. An increase in theanti-inflammatory microbiota metabolites was observed in the oral-sensitization group. CONCLUSIONS: Our study highlights the strong impact of the sensitization route on the pathophysiology and the critical phenotypic diversity of allergic asthma in a mouse model.
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spelling pubmed-100795202023-04-08 Allergic Sensitization Driving Immune Phenotyping and Disease Severity in a Mouse Model of Asthma Dijoux, Eléonore Klein, Martin Misme-Aucouturier, Barbara Cheminant, Marie-Aude de Carvalho, Marion Collin, Louise Hassoun, Dorian Delage, Erwan Gourdel, Mathilde Loirand, Gervaise Sauzeau, Vincent Magnan, Antoine Bouchaud, Grégory Allergy Asthma Immunol Res Original Article PURPOSE: Asthma is a frequent chronic inflammatory bronchial disease affecting more than 300 million patients worldwide, 70% of whom are secondary to allergy. The diversity of asthmatic endotypes contributes to their complexity. The inter-relationship between allergen and other exposure and the airway microbiome adds to the phenotypic diversity and defines the natural course of asthma. Here, we compared the mouse models of house dust mite (HDM)-induced allergic asthma. Allergic sensitization was performed via various routes and associated with outcomes. METHODS: Mice were sensitized with HDM via the oral, nasal or percutaneous routes. Lung function, barrier integrity, immune response and microbiota composition were analyzed. RESULTS: Severe impairment of respiratory function was observed in the mice sensitized by the nasal and cutaneous paths. It was associated with epithelial dysfunction characterized by an increased permeability secondary to junction protein disruption. Such sensitization paths induced a mixed eosinophilic and neutrophilic inflammatory response with high interleukin (IL)-17 airway secretion. In contrast, orally sensitized mice showed a mild impairment of respiratory function. Epithelial dysfunction was mild with increased mucus production, but preserved epithelial junctions. Regarding lung microbiota, sensitization provoked a significant loss of diversity. At the genus level, Cutibacterium, Acinetobacter, Streptococcus and Lactobacillus were found to be modulated according to the sensitization pathway. An increase in theanti-inflammatory microbiota metabolites was observed in the oral-sensitization group. CONCLUSIONS: Our study highlights the strong impact of the sensitization route on the pathophysiology and the critical phenotypic diversity of allergic asthma in a mouse model. The Korean Academy of Asthma, Allergy and Clinical Immunology; The Korean Academy of Pediatric Allergy and Respiratory Disease 2023-01-03 /pmc/articles/PMC10079520/ /pubmed/37021509 http://dx.doi.org/10.4168/aair.2023.15.2.246 Text en Copyright © 2023 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Dijoux, Eléonore
Klein, Martin
Misme-Aucouturier, Barbara
Cheminant, Marie-Aude
de Carvalho, Marion
Collin, Louise
Hassoun, Dorian
Delage, Erwan
Gourdel, Mathilde
Loirand, Gervaise
Sauzeau, Vincent
Magnan, Antoine
Bouchaud, Grégory
Allergic Sensitization Driving Immune Phenotyping and Disease Severity in a Mouse Model of Asthma
title Allergic Sensitization Driving Immune Phenotyping and Disease Severity in a Mouse Model of Asthma
title_full Allergic Sensitization Driving Immune Phenotyping and Disease Severity in a Mouse Model of Asthma
title_fullStr Allergic Sensitization Driving Immune Phenotyping and Disease Severity in a Mouse Model of Asthma
title_full_unstemmed Allergic Sensitization Driving Immune Phenotyping and Disease Severity in a Mouse Model of Asthma
title_short Allergic Sensitization Driving Immune Phenotyping and Disease Severity in a Mouse Model of Asthma
title_sort allergic sensitization driving immune phenotyping and disease severity in a mouse model of asthma
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10079520/
https://www.ncbi.nlm.nih.gov/pubmed/37021509
http://dx.doi.org/10.4168/aair.2023.15.2.246
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