Nintedanib reduces alloimmune-induced chronic airway changes in murine tracheal allografts.
Bronchiolitis obliterans
Chronic rejection
Nintedanib
Tracheal allografts
Tyrosine kinase inhibitor
Journal
Transplant immunology
ISSN: 1878-5492
Titre abrégé: Transpl Immunol
Pays: Netherlands
ID NLM: 9309923
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
received:
22
12
2021
revised:
12
04
2022
accepted:
23
04
2022
pubmed:
2
5
2022
medline:
18
6
2022
entrez:
1
5
2022
Statut:
ppublish
Résumé
The major obstacle for long-term survival after successful lung transplantation is the development of bronchiolitis obliterans (BO) which is one phenotype of chronic lung allograft dysfunction (CLAD). Nintedanib has beneficial effects treating neoplastic diseases and idiopathic pulmonary fibrosis by blocking tyrosine kinase receptors. These receptors play an important role in alloimmune-mediated proliferative diseases. The aim of this study was to determine the effect of nintedanib on proliferative airway changes after orthotopic trachea transplantation in mice. C57BL/6 mice (H-2 Tracheal allografts from mice treated with nintedanib showed significantly less features of chronic rejection than untreated allografts reflected in a higher epithelium/lamina propria ratio (ELR) [ELR: 0.65 ± 0.13 nintedanib vs. 0.50 ± 0.07 untreated controls; p < 0.05] and a reduced submucosal smooth muscle actin (SMA) content [SMA: 1.26% ± 0.78% nintedanib vs. 2.18% ± 1.01% untreated controls; p < 0.01]. Furthermore, lower T cell, macrophage and dendritic cell infiltration was detected in the nintedanib treated grafts. The protein and intragraft mRNA expression of receptor subtypes was considerably decreased in grafts of nintedanib treated mice. The mRNA expression of relevant immune mediators was affected by nintedanib treatment. Receptor blocking by nintedanib reduced alloimmune-induced inflammation and chronic airway changes in mouse trachea allografts and might be a promising approach to diminish the development of BO in lung transplants.
Sections du résumé
BACKGROUND
The major obstacle for long-term survival after successful lung transplantation is the development of bronchiolitis obliterans (BO) which is one phenotype of chronic lung allograft dysfunction (CLAD). Nintedanib has beneficial effects treating neoplastic diseases and idiopathic pulmonary fibrosis by blocking tyrosine kinase receptors. These receptors play an important role in alloimmune-mediated proliferative diseases. The aim of this study was to determine the effect of nintedanib on proliferative airway changes after orthotopic trachea transplantation in mice.
METHODS
C57BL/6 mice (H-2
RESULTS
Tracheal allografts from mice treated with nintedanib showed significantly less features of chronic rejection than untreated allografts reflected in a higher epithelium/lamina propria ratio (ELR) [ELR: 0.65 ± 0.13 nintedanib vs. 0.50 ± 0.07 untreated controls; p < 0.05] and a reduced submucosal smooth muscle actin (SMA) content [SMA: 1.26% ± 0.78% nintedanib vs. 2.18% ± 1.01% untreated controls; p < 0.01]. Furthermore, lower T cell, macrophage and dendritic cell infiltration was detected in the nintedanib treated grafts. The protein and intragraft mRNA expression of receptor subtypes was considerably decreased in grafts of nintedanib treated mice. The mRNA expression of relevant immune mediators was affected by nintedanib treatment.
CONCLUSION
Receptor blocking by nintedanib reduced alloimmune-induced inflammation and chronic airway changes in mouse trachea allografts and might be a promising approach to diminish the development of BO in lung transplants.
Identifiants
pubmed: 35490983
pii: S0966-3274(22)00082-X
doi: 10.1016/j.trim.2022.101608
pii:
doi:
Substances chimiques
Indoles
0
RNA, Messenger
0
nintedanib
G6HRD2P839
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
101608Informations de copyright
Copyright © 2022 Elsevier B.V. All rights reserved.