Differential gene analysis during the development of obliterative bronchiolitis in a murine orthotopic lung transplantation model: A comprehensive transcriptome-based analysis.
Adaptive Immunity
Animals
Bronchiolitis
/ etiology
Disease Models, Animal
Gene Expression
/ immunology
Gene Expression Profiling
Immunity, Innate
Lung
/ immunology
Lung Transplantation
Lymph Nodes
/ immunology
Male
Mice, Inbred C57BL
Minor Histocompatibility Antigens
RNA, Messenger
/ metabolism
Specific Pathogen-Free Organisms
Spleen
/ immunology
Transcriptome
Transplantation Immunology
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2020
2020
Historique:
received:
10
09
2019
accepted:
23
04
2020
entrez:
9
5
2020
pubmed:
10
5
2020
medline:
6
8
2020
Statut:
epublish
Résumé
Obliterative bronchiolitis (OB) is a known issue during minor histocompatibility antigen (mHA) disparity during lung transplantation. This study evaluated gene expression in a murine orthotropic lung transplantation model using microarray analysis. Left lungs from C57BL/10(H-2b) donor mice were transplanted into mHA-mismatched C57BL/6(H-2b) recipient mice. Three groups (OB, non-OB, and sham controls) were confirmed pathologically and analyzed. Gene expression changes in the lung grafts were determined by microarray and immunohistochemical staining, and genes were verified by quantitative PCR in the lungs and mediastinal lymph nodes (LNs). A total of 1343 genes were upregulated in the OB lungs compared to the sham group. Significant upregulation was observed for genes related to innate, e.g. Tlr2 and CCL3 and adaptive immunity, e.g. H2-ab1 and Il-21. Positive labeling for MHC class II antigen was observed in the bronchial epithelium of OB accompanied with B cells. We found increased Tlr2, Ccl3, H2-ab1, Il-21, Ighg3, Ifng, and Pdcd1 mRNA expression in the OB lung, and increased Il-21, Ighg3, and Pdcd1 expression in the OB LNs. Adaptive and innate immune reactions were involved in OB after lung transplantation, and genetic examination of related genes could be used for detection of OB.
Sections du résumé
BACKGROUND
Obliterative bronchiolitis (OB) is a known issue during minor histocompatibility antigen (mHA) disparity during lung transplantation. This study evaluated gene expression in a murine orthotropic lung transplantation model using microarray analysis.
METHODS
Left lungs from C57BL/10(H-2b) donor mice were transplanted into mHA-mismatched C57BL/6(H-2b) recipient mice. Three groups (OB, non-OB, and sham controls) were confirmed pathologically and analyzed. Gene expression changes in the lung grafts were determined by microarray and immunohistochemical staining, and genes were verified by quantitative PCR in the lungs and mediastinal lymph nodes (LNs).
RESULTS
A total of 1343 genes were upregulated in the OB lungs compared to the sham group. Significant upregulation was observed for genes related to innate, e.g. Tlr2 and CCL3 and adaptive immunity, e.g. H2-ab1 and Il-21. Positive labeling for MHC class II antigen was observed in the bronchial epithelium of OB accompanied with B cells. We found increased Tlr2, Ccl3, H2-ab1, Il-21, Ighg3, Ifng, and Pdcd1 mRNA expression in the OB lung, and increased Il-21, Ighg3, and Pdcd1 expression in the OB LNs.
CONCLUSIONS
Adaptive and innate immune reactions were involved in OB after lung transplantation, and genetic examination of related genes could be used for detection of OB.
Identifiants
pubmed: 32384121
doi: 10.1371/journal.pone.0232884
pii: PONE-D-19-24392
pmc: PMC7209239
doi:
Substances chimiques
Minor Histocompatibility Antigens
0
RNA, Messenger
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0232884Déclaration de conflit d'intérêts
I have read the journal’s policy and the authors of this manuscript have the following competing interests: TN reports personal fees from AstraZeneca, personal fees from Olympus, outside the submitted work; AK reports grants from Japan Agency for Medical Research and Development, grants from Japan Society for the Promotion of Science, grants from SRL Inc., grants from SCRUM Inc., outside the submitted work; IY reports grants from TAIHO PHARMA, grants from Pfizer, grants from Boehringer Ingelheim, grants from SHIONOGI & CO, outside the submitted work. The authors report no proprietary or commercial interest in any product mentioned or concept discussed in this article. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
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