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Airway inflammation, dysbiosis and respiratory parameters are dependent of the route of sensitization in mouse model of asthma - 09/03/22

Doi : 10.1016/j.rmr.2022.02.002 
E. Dijoux 1, 6, , L. Collin 2, 5, 6, V. Sauzeau 1, 6, G. Loirand 1, A. Magnan 3, 4, G. Bouchaud 2
1 L’institut du thorax, Inserm UMR1087, CNRS U6291, UNIV Nantes, Nantes, France 
2 INRAE UMR 1268 BIA, Nantes, France 
3 INRAE UMR 0892 VIM, Antony, France 
4 Hôpital Foch, service de pneumologie, Suresnes, France 
5 CHU Dijon Bourgogne, service de pneumologie, Dijon, France 
6 Université de Nantes, Nantes, France 

Corresponding author.

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Summary

Context

Asthma is an inflammatory chronic disease of lower part of the airways which attempt more than 300 million of asthmatics are counted in the world, whose 70% with an allergic asthma. The diversity of asthmatic endotypes contributes to its complexity. Many factors are involved in the pathophysiology of asthma to explain its phenotype diversity, as environment, the allergen sensitization pathways and the key role of microbiota. In this context, the objective of this project is to determine the influence of the sensitization pathway on the endotype and severity of asthma.

Method

Using a mouse model of dust mite allergic asthma, we analyzed respiratory function by plethysmography and by lung resistance and compliance measurement. Then we explore lung tissue damage by histological studies and we analyzed the inflammation phenotype by flow cytometry. In addition, we defined the impact of the sensitization pathway on microbiota by 16S sequencing and barrier dysfunction.

Results

Our results show an influence of the sensitization pathway on respiratory function and on the inflammatory response. Indeed, we have shown that the nasal route induces the most severe asthma with pro-Th2 inflammation with a little Th17 but rather eosinophilic asthma. The cutaneous route induces severe asthma with a mixed Th2/Th17 infiltrate. While the oral route is more tolerogenic with less impairment of respiratory function, but with an inflammatory profile of the Th2 type with eosinophilia. Concerning microbiota dysbiosis, we notified some significant difference of gut and lung phylum composition between different sensitization pathways.

Conclusions

Altogether, these results will demonstrate the link between sensitization pathway and asthmatic endotype by taking into account the mechanisms linking the immune response, the microbiota and the bronchial epithelial barrier. These results will ultimately make it possible to better target prevention strategies through immuno-intervention and the development of predictive markers and/or the selection of asthma endotypes.

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Keywords : Asthma-Allergy


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© 2022  Publié par Elsevier Masson SAS.
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Vol 39 - N° 2

P. 108 - février 2022 Retour au numéro
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