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pmid:34036106

The Potential Genes Mediate the Pathogenicity of Allogeneic CD4+T Cell in aGVHD Mouse Model.

Zhengyu Yu · Chenchen Qin · Min Cao · Xiaoya He · Hanyun Ren · Huihui Liu

BioMed research international · 2021 doi:10.1155/2021/9958745

Paper

complete

Experiment

partial

Data

partial

Analysis

partial

Execution

absent

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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pmid:34036106
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title
The Potential Genes Mediate the Pathogenicity of Allogeneic CD4+T Cell in aGVHD Mouse Model.
doi
10.1155/2021/9958745
pmid
34036106
authors array · 6 items
[0]
Zhengyu Yu
[1]
Chenchen Qin
[2]
Min Cao
[3]
Xiaoya He
[4]
Hanyun Ren
[5]
Huihui Liu
journal
BioMed research international
year
2021
abstract
Acute graft-versus-host disease (aGVHD) remains a significant and severe complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Due to the occurrence of aGVHD, allo-HSCT significantly increases the mortality rate compared with autologous hematopoietic stem cell transplantation (auto-HSCT). In this study, auto-HSCT and allo-HSCT aGVHD mouse models were built to detect the difference in CD4+ lymphocyte in different tissues based on ribonucleic acid sequencing (RNA-Seq) analysis. Clustering analysis, functional annotation, and pathway enrichment analysis were performed on differentially expressed genes (DEGs). The protein-protein interaction (PPI) network was used to find hub genes. CD4+T cells were activated by MLR and cytokine stimulation. Cells were sorted out by a flow cell sorter. The selected genes were verified by qRT-PCR, histology, and immunofluorescence staining. The GSE126518 GEO dataset was used to verify the hub genes. Enrichment analysis revealed four immune-related pathways that play an important role in aGVHD, including immunoregulatory interactions between a lymphoid and a nonlymphoid cell, chemokine receptors binding chemokines, cytokine and cytokine receptor interaction, and the chemokine signaling pathway. At the same time, with the PPI network, 11 novel hub genes that were most likely to participate in immunoregulation in aGVHD were identified, which were further validated by qRT-PCR and the GSE126518 dataset. Besides, the protein expression level of Cxcl7 was consistent with the sequencing results. In summary, this study revealed that immunoregulation-related DEGs and pathways played a vital role in the onset of aGVHD. These findings may provide some new clues for probing the pathogenesis and treatment of aGVHD.
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Early Notch signals induce a pathogenic molecular signature during priming of alloantigen-specific conventional CD4+ T cells in graft-versus-host disease
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Primers for 11 candidate immunoregulatory genes and Gapdh.
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2.10. Validation of Gene Expression by qRT-PCR
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Primers for 11 candidate immunoregulatory genes and Gapdh.
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The top 10 up- and downregulated hub genes identified in CD4+T cells from each organ.
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3.4. Potential Immunoregulatory Genes in DEGs
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The top 10 up- and downregulated hub genes identified in CD4+T cells from each organ.
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hogenicity of Allogeneic CD4+T Cell in aGVHD Mouse Model.
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34036106", "kind": "science-record", "revision": 8, "content_hash": "sha256:ee054fc29d620096b74823e24c4c1eb2ac251ab62b42a92559d03b9622b2b71b", "created_at": "2026-11-01T15:41:36Z", "updated_at": "2026-11-01T22:46:45Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "The Potential Genes Mediate the Pathogenicity of Allogeneic CD4+T Cell in aGVHD Mouse Model.", "doi": "10.1155/2021/9958745", "pmid": "34036106", "authors": ["Zhengyu Yu", "Chenchen Qin", "Min Cao", "Xiaoya He", "Hanyun Ren", "Huihui Liu"], "journal": "BioMed research international", "year": 2021, "abstract": "Acute graft-versus-host disease (aGVHD) remains a significant and severe complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Due to the occurrence of aGVHD, allo-HSCT significantly increases the mortality rate compared with autologous hematopoietic stem cell transplantation (auto-HSCT). In this study, auto-HSCT and allo-HSCT aGVHD mouse models were built to detect the difference in CD4+ lymphocyte in different tissues based on ribonucleic acid sequencing (RNA-Seq) analysis. Clustering analysis, functional annotation, and pathway enrichment analysis were performed on differentially expressed genes (DEGs). The protein-protein interaction (PPI) network was used to find hub genes. CD4+T cells were activated by MLR and cytokine stimulation. Cells were sorted out by a flow cell sorter. The selected genes were verified by qRT-PCR, histology, and immunofluorescence staining. The GSE126518 GEO dataset was used to verify the hub genes. Enrichment analysis revealed four immune-related pathways that play an important role in aGVHD, including immunoregulatory interactions between a lymphoid and a nonlymphoid cell, chemokine receptors binding chemokines, cytokine and cytokine receptor interaction, and the chemokine signaling pathway. At the same time, with the PPI network, 11 novel hub genes that were most likely to participate in immunoregulation in aGVHD were identified, which were further validated by qRT-PCR and the GSE126518 dataset. Besides, the protein expression level of Cxcl7 was consistent with the sequencing results. In summary, this study revealed that immunoregulation-related DEGs and pathways played a vital role in the onset of aGVHD. These findings may provide some new clues for probing the pathogenesis and treatment of aGVHD.", "claims": [{"id": "claim-data-access", "statement": "All the data of this study are openly available upon request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34036106", "locator": "sections[29] \"Data Availability\" paragraph 2", "quote": "All the data of this study are openly available upon request."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:34036106"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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Validation of Gene Expression by qRT-PCR", "row_count": 13, "column_count": 4}, "table": {"label": "Table 1", "caption": "Primers for 11 candidate immunoregulatory genes and Gapdh.", "rows": [["Gene", "Forward primer (5′ → 3′)", "Reverse primer (5′ → 3′)", "Product length"], ["Cxcl7", "CTCACGTTGTTCCCTCCTGG", "TGGGTCCATGCCATCAGATT", "192"], ["S1pr3", "TCAACACTCTTCCCGCAGTC", "CCCGGAGAGTGTCATTTCCC", "192"], ["Npy", "TAACAAGCGAATGGGGCTGT", "TGATGTAGTGTCGCAGAGCG", "61"], ["Hebp1", "CCTGTCTACTCACGCGCTTA", "GGAGACATCTTCCTTGCCCC", "180"], ["Rgs1", "TGCCAACCAGACAGGTCAAA", "TTCACAGCATCTGAATGCACAA", "171"], ["Fpr2", "TTCATGGGCCAGGACTTTCG", "CACAGACTTCATGGGGCCTT", "155"], ["Cxcl16", "GGGCTTTGGACCCTTGTCTC", "GATCCAAAGTACCCTGCGGT", "152"], ["Ccl9", "CAGGCCGGGCATCATCTTTA", "AGTAGCTGGCAGTTCACACC", "165"], ["Cxcl3", "CTGCACCCAGACAGAAGTCAT", "CCGTTGGGATGGATCGCTTT", "198"], ["Plg", "TCCGTGGGTTGGATGTTCAG", "ATTGTCCGGTCAGCAACCAT", "163"], ["Kng1", "TCCCGACTGTGAAATGCCAA", "CCCAGTGTCATATGGTGGGG", "164"], ["Gapdh", "CTCATGACCACAGTCCATGC", "CACATTGGGGGTAGGAACAC", "201"]], "row_count": 13, "column_count": 4, "numeric_cells": 15, "header_rows": 1, "locator": "section[12]/table-wrap[1]#tab1"}}, {"id": "asset:table:pmid:34036106:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:3b8939455f76b6d79f1c6f49bba848a92f6e3c3d2879a2f41c6803bc9f61c49b", "bytes": 855, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[22]/table-wrap[1]#tab2", "version": null, "note": "The top 10 up- and downregulated hub genes identified in CD4+T cells from each organ.", "structure": {"pmcid": "PMC8121574", "section_index": 22, "section_title": "3.4. Potential Immunoregulatory Genes in DEGs", "row_count": 7, "column_count": 3}, "table": {"label": "Table 2", "caption": "The top 10 up- and downregulated hub genes identified in CD4+T cells from each organ.", "rows": [["Group", "Hub gene"], ["Allospleen vs. autospleen", "Upregulated", "Cxcr2, Ccr1, Ccl5, Rgs1, Cxcl10, Cxcr5, Cxcr6, Cxcl2, Cxcl9, and Fpr2"], ["Downregulated", "Ccr7, Cxcl7, Ccr6, Ccr4, Sstr2, Penk, S1pr3, Npy, Hebp1, and Flt3"], ["Alloliver vs. autospleen", "Upregulated", "Kng1, Plg, Rdh7, Cps1, Serpinc1, Apof, Uox, Fga, Apoc3, and Hpx"], ["Downregulated", "Ccr7, Cxcr4, Ccr3, Ccr4, Htr1b, Ccr6, Cxcl7, S1pr3, Npy, and Ptger3"], ["Allolung vs. autospleen", "Upregulated", "C3, Cxcl16, Ccl9, Ccr1, Cxcr2, Cxcl5, Cxcl3, Cxcl1, Ccr8, and Cxcl10"], ["Downregulated", "Ccnb1, Cdc20, Aurkb, Aurka, Plk1, Bub1b, Mcm2, Cdc6, Mcm5, and Cdk1"]], "row_count": 7, "column_count": 3, "numeric_cells": 3, "header_rows": 1, "locator": "section[22]/table-wrap[1]#tab2"}}], "gaps": 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