Identification of Pro-Fibrotic Macrophage Populations by Single-Cell Transcriptomic Analysis in West Highland White Terriers Affected With Canine Idiopathic Pulmonary Fibrosis.
bronchoalveolar lavage fluid
canine idiopathic pulmonary fibrosis
dog
lung
macrophages
single-cell RNA-sequencing methods
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2020
2020
Historique:
received:
29
09
2020
accepted:
17
11
2020
entrez:
1
1
2021
pubmed:
2
1
2021
medline:
23
6
2021
Statut:
epublish
Résumé
Canine idiopathic pulmonary fibrosis (CIPF) affects old dogs from the West Highland white terrier (WHWT) breed and mimics idiopathic pulmonary fibrosis (IPF) in human. The disease results from deposition of fibrotic tissue in the lung parenchyma causing respiratory failure. Recent studies in IPF using single-cell RNA sequencing (scRNA-seq) revealed the presence of profibrotic macrophage populations in the lung, which could be targeted for therapeutic purpose. In dogs, scRNA-seq was recently validated for the detection of cell populations in bronchoalveolar lavage fluid (BALF) from healthy dogs. Here we used the scRNA-seq to characterize disease-related heterogeneity within cell populations of macrophages/monocytes (Ma/Mo) in the BALF from five WHWTs affected with CIPF in comparison with three healthy WHWTs. Gene set enrichment analysis was also used to assess pro-fibrotic capacities of Ma/Mo populations. Five clusters of Ma/Mo were identified. Gene set enrichment analyses revealed the presence of pro-fibrotic monocytes in higher proportion in CIPF WHWTs than in healthy WHWTs. In addition, monocyte-derived macrophages enriched in pro-fibrotic genes in CIPF compared with healthy WHWTs were also identified. These results suggest the implication of Ma/Mo clusters in CIPF processes, although, further research is needed to understand their role in disease pathogenesis. Overexpressed molecules associated with pulmonary fibrosis processes were also identified that could be used as biomarkers and/or therapeutic targets in the future.
Identifiants
pubmed: 33384697
doi: 10.3389/fimmu.2020.611749
pmc: PMC7770158
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
611749Informations de copyright
Copyright © 2020 Fastrès, Pirottin, Fievez, Tutunaru, Bolen, Merveille, Marichal, Desmet, Bureau and Clercx.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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