The transition from normal lung anatomy to minimal and established fibrosis in idiopathic pulmonary fibrosis (IPF).
Aged
Animals
Biomarkers
Disease Progression
Disease Susceptibility
Female
Gene Expression
Gene Expression Profiling
Humans
Idiopathic Pulmonary Fibrosis
/ diagnosis
Immunohistochemistry
Inflammation Mediators
/ metabolism
Lung
/ diagnostic imaging
Male
Mice
Middle Aged
Models, Biological
Preoperative Period
Tomography, X-Ray Computed
IPF
Integrative analysis
MDCT
Micro-CT
Quantitative histology
RNAseq
Journal
EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039
Informations de publication
Date de publication:
Apr 2021
Apr 2021
Historique:
received:
16
01
2021
revised:
12
03
2021
accepted:
19
03
2021
pubmed:
17
4
2021
medline:
30
11
2021
entrez:
16
4
2021
Statut:
ppublish
Résumé
The transition from normal lung anatomy to minimal and established fibrosis is an important feature of the pathology of idiopathic pulmonary fibrosis (IPF). The purpose of this report is to examine the molecular and cellular mechanisms associated with this transition. Pre-operative thoracic Multidetector Computed Tomography (MDCT) scans of patients with severe IPF (n = 9) were used to identify regions of minimal(n = 27) and established fibrosis(n = 27). MDCT, Micro-CT, quantitative histology, and next-generation sequencing were used to compare 24 samples from donor controls (n = 4) to minimal and established fibrosis samples. The present results extended earlier reports about the transition from normal lung anatomy to minimal and established fibrosis by showing that there are activations of TGFBI, T cell co-stimulatory genes, and the down-regulation of inhibitory immune-checkpoint genes compared to controls. The expression patterns of these genes indicated activation of a field immune response, which is further supported by the increased infiltration of inflammatory immune cells dominated by lymphocytes that are capable of forming lymphoid follicles. Moreover, fibrosis pathways, mucin secretion, surfactant, TLRs, and cytokine storm-related genes also participate in the transitions from normal lung anatomy to minimal and established fibrosis. The transition from normal lung anatomy to minimal and established fibrosis is associated with genes that are involved in the tissue repair processes, the activation of immune responses as well as the increased infiltration of CD4, CD8, B cell lymphocytes, and macrophages. These molecular and cellular events correlate with the development of structural abnormality of IPF and probably contribute to its pathogenesis.
Sections du résumé
BACKGROUND
BACKGROUND
The transition from normal lung anatomy to minimal and established fibrosis is an important feature of the pathology of idiopathic pulmonary fibrosis (IPF). The purpose of this report is to examine the molecular and cellular mechanisms associated with this transition.
METHODS
METHODS
Pre-operative thoracic Multidetector Computed Tomography (MDCT) scans of patients with severe IPF (n = 9) were used to identify regions of minimal(n = 27) and established fibrosis(n = 27). MDCT, Micro-CT, quantitative histology, and next-generation sequencing were used to compare 24 samples from donor controls (n = 4) to minimal and established fibrosis samples.
FINDINGS
RESULTS
The present results extended earlier reports about the transition from normal lung anatomy to minimal and established fibrosis by showing that there are activations of TGFBI, T cell co-stimulatory genes, and the down-regulation of inhibitory immune-checkpoint genes compared to controls. The expression patterns of these genes indicated activation of a field immune response, which is further supported by the increased infiltration of inflammatory immune cells dominated by lymphocytes that are capable of forming lymphoid follicles. Moreover, fibrosis pathways, mucin secretion, surfactant, TLRs, and cytokine storm-related genes also participate in the transitions from normal lung anatomy to minimal and established fibrosis.
INTERPRETATION
CONCLUSIONS
The transition from normal lung anatomy to minimal and established fibrosis is associated with genes that are involved in the tissue repair processes, the activation of immune responses as well as the increased infiltration of CD4, CD8, B cell lymphocytes, and macrophages. These molecular and cellular events correlate with the development of structural abnormality of IPF and probably contribute to its pathogenesis.
Identifiants
pubmed: 33862585
pii: S2352-3964(21)00118-3
doi: 10.1016/j.ebiom.2021.103325
pmc: PMC8054143
pii:
doi:
Substances chimiques
Biomarkers
0
Inflammation Mediators
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
103325Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest All other authors declare no competing interests.