Computational Analysis Reveals the Characteristics of Immune Cells in Glomerular and Tubulointerstitial Compartments in IgA Nephropathy Patients
Objective: The commonalities and differences regarding immune states between glomerular and tubulointerstitial compartments of IgA nephropathy (IgAN) remains largely undetermined. We aim to perform bioinformatic analysis for providing a comprehensive insight into the characteristics of immune cells...
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| Format: | Article |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.838863/full |
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| author | Bin Li Bin Li Suchun Li Suchun Li Yuting Fan Yuting Fan Hui Diao Hui Diao Siyang Ye Siyang Ye Huajing Peng Huajing Peng Wei Chen Wei Chen |
| author_facet | Bin Li Bin Li Suchun Li Suchun Li Yuting Fan Yuting Fan Hui Diao Hui Diao Siyang Ye Siyang Ye Huajing Peng Huajing Peng Wei Chen Wei Chen |
| author_sort | Bin Li |
| collection | DOAJ |
| description | Objective: The commonalities and differences regarding immune states between glomerular and tubulointerstitial compartments of IgA nephropathy (IgAN) remains largely undetermined. We aim to perform bioinformatic analysis for providing a comprehensive insight into the characteristics of immune cells and associated molecular mechanisms in IgAN.Materials and Methods: We performed integrated bioinformatic analyses by using IgAN-related datasets from the Gene Expression Omnibus database. First, the differentially expressed genes (DEGs) were identified and subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Then, CIBERSORT was employed to determine the landscape of infiltrating immune cells in both glomerular and tubulointerstitial compartments of IgAN patients, followed by Pearson’s correlation analysis and principal component analysis (PCA). Finally, commonly shared DEGs between glomerular and tubulointerstitial entities were recognized, followed by correlation analyses to identify the dominant commonly shared DEGs associated with immune cell infiltration in IgAN.Results: GO and KEGG enrichment analyses showed apparently distinct biological processes in the glomerular and tubulointerstitial compartments of IgAN. In addition, CIBERSORT analyses revealed a clear trend of increasing proportions of M1 macrophage and M2 macrophage in the glomerular compartment while noticeably higher proportions of resting CD4+ memory T cells and M2 macrophages in the tubulointerstitial compartments. The PCA analyses showed that the varying composition of immune cells in both glomerular and tubulointerstitial entities was compelling to distinguish IgAN patients from healthy living controls. In addition, 21 commonly shared DEGs between glomerular and tubulointerstitial entities were recognized as key regulators in the pathogenesis of IgAN, among which the enhanced hemoglobin subunit beta (HBB) gene expression was found to be positively associated with M2 macrophage in the glomerular compartment and resting CD4+ memory T cells in the tubulointerstitial compartment. Most importantly, FBJ murine osteosarcoma viral oncogene homolog B (FOSB) gene deficiency was recognized as the dominant alteration in promoting M2 macrophage infiltration in the glomerular compartment of IgAN.Conclusion: The findings from our current study for the first time reveal commonalities and differences regarding immune states between glomerular and tubulointerstitial compartments, as well as decode the essential role of M2 macrophages and associated molecular patterns within the microenvironments of IgAN. |
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| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-10T09:20:30Z |
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| series | Frontiers in Genetics |
| spelling | doaj.art-b505cdd165bd4bf1a867ffaf76d186462022-12-22T01:54:42ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-05-011310.3389/fgene.2022.838863838863Computational Analysis Reveals the Characteristics of Immune Cells in Glomerular and Tubulointerstitial Compartments in IgA Nephropathy PatientsBin Li0Bin Li1Suchun Li2Suchun Li3Yuting Fan4Yuting Fan5Hui Diao6Hui Diao7Siyang Ye8Siyang Ye9Huajing Peng10Huajing Peng11Wei Chen12Wei Chen13Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaNHC Key Laboratory of Clinical Nephrology (Sun Yat-Sen University), Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, ChinaDepartment of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaNHC Key Laboratory of Clinical Nephrology (Sun Yat-Sen University), Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, ChinaDepartment of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaNHC Key Laboratory of Clinical Nephrology (Sun Yat-Sen University), Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, ChinaDepartment of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaNHC Key Laboratory of Clinical Nephrology (Sun Yat-Sen University), Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, ChinaDepartment of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaNHC Key Laboratory of Clinical Nephrology (Sun Yat-Sen University), Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, ChinaDepartment of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaNHC Key Laboratory of Clinical Nephrology (Sun Yat-Sen University), Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, ChinaDepartment of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaNHC Key Laboratory of Clinical Nephrology (Sun Yat-Sen University), Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, ChinaObjective: The commonalities and differences regarding immune states between glomerular and tubulointerstitial compartments of IgA nephropathy (IgAN) remains largely undetermined. We aim to perform bioinformatic analysis for providing a comprehensive insight into the characteristics of immune cells and associated molecular mechanisms in IgAN.Materials and Methods: We performed integrated bioinformatic analyses by using IgAN-related datasets from the Gene Expression Omnibus database. First, the differentially expressed genes (DEGs) were identified and subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Then, CIBERSORT was employed to determine the landscape of infiltrating immune cells in both glomerular and tubulointerstitial compartments of IgAN patients, followed by Pearson’s correlation analysis and principal component analysis (PCA). Finally, commonly shared DEGs between glomerular and tubulointerstitial entities were recognized, followed by correlation analyses to identify the dominant commonly shared DEGs associated with immune cell infiltration in IgAN.Results: GO and KEGG enrichment analyses showed apparently distinct biological processes in the glomerular and tubulointerstitial compartments of IgAN. In addition, CIBERSORT analyses revealed a clear trend of increasing proportions of M1 macrophage and M2 macrophage in the glomerular compartment while noticeably higher proportions of resting CD4+ memory T cells and M2 macrophages in the tubulointerstitial compartments. The PCA analyses showed that the varying composition of immune cells in both glomerular and tubulointerstitial entities was compelling to distinguish IgAN patients from healthy living controls. In addition, 21 commonly shared DEGs between glomerular and tubulointerstitial entities were recognized as key regulators in the pathogenesis of IgAN, among which the enhanced hemoglobin subunit beta (HBB) gene expression was found to be positively associated with M2 macrophage in the glomerular compartment and resting CD4+ memory T cells in the tubulointerstitial compartment. Most importantly, FBJ murine osteosarcoma viral oncogene homolog B (FOSB) gene deficiency was recognized as the dominant alteration in promoting M2 macrophage infiltration in the glomerular compartment of IgAN.Conclusion: The findings from our current study for the first time reveal commonalities and differences regarding immune states between glomerular and tubulointerstitial compartments, as well as decode the essential role of M2 macrophages and associated molecular patterns within the microenvironments of IgAN.https://www.frontiersin.org/articles/10.3389/fgene.2022.838863/fullIgA nephropathyglomerulonephritisimmune cell landscapemacrophagesCIBERSORTbioinformatic analysis |
| spellingShingle | Bin Li Bin Li Suchun Li Suchun Li Yuting Fan Yuting Fan Hui Diao Hui Diao Siyang Ye Siyang Ye Huajing Peng Huajing Peng Wei Chen Wei Chen Computational Analysis Reveals the Characteristics of Immune Cells in Glomerular and Tubulointerstitial Compartments in IgA Nephropathy Patients Frontiers in Genetics IgA nephropathy glomerulonephritis immune cell landscape macrophages CIBERSORT bioinformatic analysis |
| title | Computational Analysis Reveals the Characteristics of Immune Cells in Glomerular and Tubulointerstitial Compartments in IgA Nephropathy Patients |
| title_full | Computational Analysis Reveals the Characteristics of Immune Cells in Glomerular and Tubulointerstitial Compartments in IgA Nephropathy Patients |
| title_fullStr | Computational Analysis Reveals the Characteristics of Immune Cells in Glomerular and Tubulointerstitial Compartments in IgA Nephropathy Patients |
| title_full_unstemmed | Computational Analysis Reveals the Characteristics of Immune Cells in Glomerular and Tubulointerstitial Compartments in IgA Nephropathy Patients |
| title_short | Computational Analysis Reveals the Characteristics of Immune Cells in Glomerular and Tubulointerstitial Compartments in IgA Nephropathy Patients |
| title_sort | computational analysis reveals the characteristics of immune cells in glomerular and tubulointerstitial compartments in iga nephropathy patients |
| topic | IgA nephropathy glomerulonephritis immune cell landscape macrophages CIBERSORT bioinformatic analysis |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.838863/full |
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