Integrative analysis of single-cell and bulk transcriptome data reveal the significant role of macrophages in lupus nephritis
Objective We attempted to identify abnormal immune cell components and signaling pathways in lupus nephritis (LN) and to identify potential therapeutic targets. Methods Differentially expressed genes (DEGs) between LN and normal kidney tissues were identified from bulk transcriptome data, and functional annotation was performed. The phenotypic changes in macrophages and aberrant intercellular signaling communications within immune cells were imputed from LN scRNA-seq data using trajectory analysis and verified using immunofluorescence staining. Finally, lentivirus-mediated overexpression of LGALS9, the gene encoding Galectin 9, in THP-1 cells was used to study the functional effect of this gene on monocytic cells. Results From bulk transcriptome data, a significant activation of interferon (IFN) signaling was observed, and its intensity showed a significantly positive correlation with the abundance of infiltrating macrophages in LN. Analysis of scRNA-seq data revealed 17 immune cell clusters, with macrophages showing the highest enrichment of intercellular signal communication in LN. Trajectory analysis revealed macrophages in LN undergo a phenotypic change from inflammatory patrolling macrophages to phagocytic and then to antigen-presenting macrophages, and secrete various pro-inflammatory factors and complement components. LGALS9 was found significantly upregulated in macrophages in LN, which was confirmed by the immunofluorescence assay. Gene functional study showed that LGALS9 overexpression in THP-1 cells significantly elicited pro-inflammatory activation, releasing multiple immune cell chemoattractants. Conclusion Our results present an important pathophysiological role for macrophages in LN, and our preliminary results demonstrate significant pro-inflammatory effects of LGALS9 gene in LN macrophages..
Key message Macrophages were found massively infiltrate in the parenchyma of LN kidney. Macrophages play a vital role in aberrant intercellular signaling in LN and undergo a significant phenotypic evolution in LN. This study suggests for the first time that LGALS9 could be a potential druggable target in macrophage targeting strategy in treating LN..
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:26 |
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| Enthalten in: |
Arthritis Research & Therapy - 26(2024), 1 vom: 12. Apr. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wei, Shuping [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| Themen: |
Infiltrating immune cells |
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| Anmerkungen: |
© The Author(s) 2024 |
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| doi: |
10.1186/s13075-024-03311-y |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
SPR055504027 |
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| 520 | |a Objective We attempted to identify abnormal immune cell components and signaling pathways in lupus nephritis (LN) and to identify potential therapeutic targets. Methods Differentially expressed genes (DEGs) between LN and normal kidney tissues were identified from bulk transcriptome data, and functional annotation was performed. The phenotypic changes in macrophages and aberrant intercellular signaling communications within immune cells were imputed from LN scRNA-seq data using trajectory analysis and verified using immunofluorescence staining. Finally, lentivirus-mediated overexpression of LGALS9, the gene encoding Galectin 9, in THP-1 cells was used to study the functional effect of this gene on monocytic cells. Results From bulk transcriptome data, a significant activation of interferon (IFN) signaling was observed, and its intensity showed a significantly positive correlation with the abundance of infiltrating macrophages in LN. Analysis of scRNA-seq data revealed 17 immune cell clusters, with macrophages showing the highest enrichment of intercellular signal communication in LN. Trajectory analysis revealed macrophages in LN undergo a phenotypic change from inflammatory patrolling macrophages to phagocytic and then to antigen-presenting macrophages, and secrete various pro-inflammatory factors and complement components. LGALS9 was found significantly upregulated in macrophages in LN, which was confirmed by the immunofluorescence assay. Gene functional study showed that LGALS9 overexpression in THP-1 cells significantly elicited pro-inflammatory activation, releasing multiple immune cell chemoattractants. Conclusion Our results present an important pathophysiological role for macrophages in LN, and our preliminary results demonstrate significant pro-inflammatory effects of LGALS9 gene in LN macrophages. | ||
| 520 | |a Key message Macrophages were found massively infiltrate in the parenchyma of LN kidney. Macrophages play a vital role in aberrant intercellular signaling in LN and undergo a significant phenotypic evolution in LN. This study suggests for the first time that LGALS9 could be a potential druggable target in macrophage targeting strategy in treating LN. | ||
| 650 | 4 | |a Lupus nephritis |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a ScRNA-seq |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Infiltrating immune cells |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Macrophages |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a LGALS9 |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Shen, Haiyun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yidan |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Chunrui |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Shoushan |e verfasserin |4 aut | |
| 700 | 1 | |a Yao, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Jin, Zhibin |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Hongliang |e verfasserin |4 aut | |
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