Transcriptomic analysis of graft liver provides insight into the immune response of rat liver transplantation

BackgroundAs an “immune-privileged organ”, the liver has higher rates of both spontaneous tolerance and operational tolerance after being transplanted compared with other solid organs. Also, a large number of patients still need to take long-term immunosuppression regimens. Liver transplantation (LT...

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Main Authors: Wanyue Cao, Jing Lu, Shanbao Li, Fangbin Song, Junming Xu
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-11-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2022.947437/full
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author Wanyue Cao
Jing Lu
Shanbao Li
Fangbin Song
Junming Xu
author_facet Wanyue Cao
Jing Lu
Shanbao Li
Fangbin Song
Junming Xu
author_sort Wanyue Cao
collection DOAJ
description BackgroundAs an “immune-privileged organ”, the liver has higher rates of both spontaneous tolerance and operational tolerance after being transplanted compared with other solid organs. Also, a large number of patients still need to take long-term immunosuppression regimens. Liver transplantation (LT) rejection involves varieties of pathophysiological processes and cell types, and a deeper understanding of LT immune response is urgently needed.MethodsHomogenic and allogeneic rat LT models were established, and recipient tissue was collected on postoperative day 7. The degree of LT rejection was evaluated by liver pathological changes and liver function. Differentially expressed genes (DEGs) were detected by transcriptome sequencing and confirmed by reverse transcription-polymerase chain reaction. The functional properties of DEGs were characterized by the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome pathway analyses. The cells infiltrating the graft and recipient spleen and peripheral blood were evaluated by immunofluorescence and flow cytometry.ResultA total of 1,465 DEGs were screened, including 1,177 up-regulated genes and 288 down-regulated genes. GO enrichment and KEGG pathway analysis indicated that DEGs were involved in several immunobiological processes, including T cell activation, Th1, Th2 and Th17 cell differentiation, cytokine-cytokine receptor interaction and other immune processes. Reactome results showed that PD-1 signaling was enriched. Further research confirmed that mRNA expression of multiple immune cell markers increased and markers of T cell exhaustion significantly changed. Flow cytometry showed that the proportion of Treg decreased, and that of PD-1+CD4+ T cells and PD-1+CD8+ T cells increased in the allogeneic group.ConclusionUsing an omic approach, we revealed that the development of LT rejection involved multiple immune cells, activation of various immune pathways, and specific alterations of immune checkpoints, which would benefit risk assessment in the clinic and understanding of pathogenesis regarding LT tolerance. Further clinical validations are warranted for our findings.
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spelling doaj.art-3472aa02927a48b1b1d1368e93e188f02022-12-22T04:38:04ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-11-011310.3389/fimmu.2022.947437947437Transcriptomic analysis of graft liver provides insight into the immune response of rat liver transplantationWanyue CaoJing LuShanbao LiFangbin SongJunming XuBackgroundAs an “immune-privileged organ”, the liver has higher rates of both spontaneous tolerance and operational tolerance after being transplanted compared with other solid organs. Also, a large number of patients still need to take long-term immunosuppression regimens. Liver transplantation (LT) rejection involves varieties of pathophysiological processes and cell types, and a deeper understanding of LT immune response is urgently needed.MethodsHomogenic and allogeneic rat LT models were established, and recipient tissue was collected on postoperative day 7. The degree of LT rejection was evaluated by liver pathological changes and liver function. Differentially expressed genes (DEGs) were detected by transcriptome sequencing and confirmed by reverse transcription-polymerase chain reaction. The functional properties of DEGs were characterized by the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome pathway analyses. The cells infiltrating the graft and recipient spleen and peripheral blood were evaluated by immunofluorescence and flow cytometry.ResultA total of 1,465 DEGs were screened, including 1,177 up-regulated genes and 288 down-regulated genes. GO enrichment and KEGG pathway analysis indicated that DEGs were involved in several immunobiological processes, including T cell activation, Th1, Th2 and Th17 cell differentiation, cytokine-cytokine receptor interaction and other immune processes. Reactome results showed that PD-1 signaling was enriched. Further research confirmed that mRNA expression of multiple immune cell markers increased and markers of T cell exhaustion significantly changed. Flow cytometry showed that the proportion of Treg decreased, and that of PD-1+CD4+ T cells and PD-1+CD8+ T cells increased in the allogeneic group.ConclusionUsing an omic approach, we revealed that the development of LT rejection involved multiple immune cells, activation of various immune pathways, and specific alterations of immune checkpoints, which would benefit risk assessment in the clinic and understanding of pathogenesis regarding LT tolerance. Further clinical validations are warranted for our findings.https://www.frontiersin.org/articles/10.3389/fimmu.2022.947437/fullRNA-seqliver transplantationregulatory T cellsimmune checkpointdifferentially expressed genesGO
spellingShingle Wanyue Cao
Jing Lu
Shanbao Li
Fangbin Song
Junming Xu
Transcriptomic analysis of graft liver provides insight into the immune response of rat liver transplantation
Frontiers in Immunology
RNA-seq
liver transplantation
regulatory T cells
immune checkpoint
differentially expressed genes
GO
title Transcriptomic analysis of graft liver provides insight into the immune response of rat liver transplantation
title_full Transcriptomic analysis of graft liver provides insight into the immune response of rat liver transplantation
title_fullStr Transcriptomic analysis of graft liver provides insight into the immune response of rat liver transplantation
title_full_unstemmed Transcriptomic analysis of graft liver provides insight into the immune response of rat liver transplantation
title_short Transcriptomic analysis of graft liver provides insight into the immune response of rat liver transplantation
title_sort transcriptomic analysis of graft liver provides insight into the immune response of rat liver transplantation
topic RNA-seq
liver transplantation
regulatory T cells
immune checkpoint
differentially expressed genes
GO
url https://www.frontiersin.org/articles/10.3389/fimmu.2022.947437/full
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AT fangbinsong transcriptomicanalysisofgraftliverprovidesinsightintotheimmuneresponseofratlivertransplantation
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