Exploring the shared mechanism of fatigue between systemic lupus erythematosus and myalgic encephalomyelitis/chronic fatigue syndrome: monocytic dysregulation and drug repurposing
BackgroundSLE and ME/CFS both present significant fatigue and share immune dysregulation. The mechanisms underlying fatigue in these disorders remain unclear, and there are no standardized treatments. This study aims to explore shared mechanisms and predict potential therapeutic drugs for fatigue in...
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| Language: | English |
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1440922/full |
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| author | Daisi Zheng Xiaolong Li Peicheng Wang Qingmiao Zhu Zhiyan Huang Ting Zhao |
| author_facet | Daisi Zheng Xiaolong Li Peicheng Wang Qingmiao Zhu Zhiyan Huang Ting Zhao |
| author_sort | Daisi Zheng |
| collection | DOAJ |
| description | BackgroundSLE and ME/CFS both present significant fatigue and share immune dysregulation. The mechanisms underlying fatigue in these disorders remain unclear, and there are no standardized treatments. This study aims to explore shared mechanisms and predict potential therapeutic drugs for fatigue in SLE and ME/CFS.MethodsGenes associated with SLE and ME/CFS were collected from disease target and clinical sample databases to identify overlapping genes. Bioinformatics analyses, including GO, KEGG, PPI network construction, and key target identification, were performed. ROC curve and correlation analysis of key targets, along with single-cell clustering, were conducted to validate their expression in different cell types. Additionally, an inflammation model was established using THP-1 cells to simulate monocyte activation in both diseases in vitro, and RT-qPCR was used to validate the expression of the key targets. A TF-mRNA-miRNA co-regulatory network was constructed, followed by drug prediction and molecular docking.ResultsFifty-eight overlapping genes were identified, mainly involved in innate immunity and inflammation. Five key targets were identified (IL1β, CCL2, TLR2, STAT1, IFIH1). Single-cell sequencing revealed that monocytes are enriched with these targets. RT-qPCR confirmed significant upregulation of these targets in the model group. A co-regulatory network was constructed, and ten potential drugs, including suloctidil, N-Acetyl-L-cysteine, simvastatin, ACMC-20mvek, and camptothecin, were predicted. Simvastatin and camptothecin showed high affinity for the key targets.ConclusionSLE and ME/CFS share immune and inflammatory pathways. The identified key targets are predominantly enriched in monocytes at the single-cell level, suggesting that classical monocytes may be crucial in linking inflammation and fatigue. RT-qPCR confirmed upregulation in activated monocytes. The TF-mRNA-miRNA network provides a foundation for future research, and drug prediction suggests N-Acetyl-L-cysteine and camptothecin as potential therapies. |
| format | Article |
| id | doaj-art-da547da535304b518bc27c51e88253b0 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-da547da535304b518bc27c51e88253b02025-01-07T06:40:32ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.14409221440922Exploring the shared mechanism of fatigue between systemic lupus erythematosus and myalgic encephalomyelitis/chronic fatigue syndrome: monocytic dysregulation and drug repurposingDaisi Zheng0Xiaolong Li1Peicheng Wang2Qingmiao Zhu3Zhiyan Huang4Ting Zhao5The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, ChinaCollege of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, ChinaThe First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, ChinaCollege of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, ChinaThe First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, ChinaKey Laboratory of Chinese Medicine Rheumatology of Zhejiang Province, Research Institute of Chinese Medical Clinical Foundation and Immunology, College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, ChinaBackgroundSLE and ME/CFS both present significant fatigue and share immune dysregulation. The mechanisms underlying fatigue in these disorders remain unclear, and there are no standardized treatments. This study aims to explore shared mechanisms and predict potential therapeutic drugs for fatigue in SLE and ME/CFS.MethodsGenes associated with SLE and ME/CFS were collected from disease target and clinical sample databases to identify overlapping genes. Bioinformatics analyses, including GO, KEGG, PPI network construction, and key target identification, were performed. ROC curve and correlation analysis of key targets, along with single-cell clustering, were conducted to validate their expression in different cell types. Additionally, an inflammation model was established using THP-1 cells to simulate monocyte activation in both diseases in vitro, and RT-qPCR was used to validate the expression of the key targets. A TF-mRNA-miRNA co-regulatory network was constructed, followed by drug prediction and molecular docking.ResultsFifty-eight overlapping genes were identified, mainly involved in innate immunity and inflammation. Five key targets were identified (IL1β, CCL2, TLR2, STAT1, IFIH1). Single-cell sequencing revealed that monocytes are enriched with these targets. RT-qPCR confirmed significant upregulation of these targets in the model group. A co-regulatory network was constructed, and ten potential drugs, including suloctidil, N-Acetyl-L-cysteine, simvastatin, ACMC-20mvek, and camptothecin, were predicted. Simvastatin and camptothecin showed high affinity for the key targets.ConclusionSLE and ME/CFS share immune and inflammatory pathways. The identified key targets are predominantly enriched in monocytes at the single-cell level, suggesting that classical monocytes may be crucial in linking inflammation and fatigue. RT-qPCR confirmed upregulation in activated monocytes. The TF-mRNA-miRNA network provides a foundation for future research, and drug prediction suggests N-Acetyl-L-cysteine and camptothecin as potential therapies.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1440922/fullsystemic lupus erythematosusmyalgic encephalomyelitis/chronic fatigue syndromefatiguebioinformatics analysissingle-cell transcriptomics |
| spellingShingle | Daisi Zheng Xiaolong Li Peicheng Wang Qingmiao Zhu Zhiyan Huang Ting Zhao Exploring the shared mechanism of fatigue between systemic lupus erythematosus and myalgic encephalomyelitis/chronic fatigue syndrome: monocytic dysregulation and drug repurposing Frontiers in Immunology systemic lupus erythematosus myalgic encephalomyelitis/chronic fatigue syndrome fatigue bioinformatics analysis single-cell transcriptomics |
| title | Exploring the shared mechanism of fatigue between systemic lupus erythematosus and myalgic encephalomyelitis/chronic fatigue syndrome: monocytic dysregulation and drug repurposing |
| title_full | Exploring the shared mechanism of fatigue between systemic lupus erythematosus and myalgic encephalomyelitis/chronic fatigue syndrome: monocytic dysregulation and drug repurposing |
| title_fullStr | Exploring the shared mechanism of fatigue between systemic lupus erythematosus and myalgic encephalomyelitis/chronic fatigue syndrome: monocytic dysregulation and drug repurposing |
| title_full_unstemmed | Exploring the shared mechanism of fatigue between systemic lupus erythematosus and myalgic encephalomyelitis/chronic fatigue syndrome: monocytic dysregulation and drug repurposing |
| title_short | Exploring the shared mechanism of fatigue between systemic lupus erythematosus and myalgic encephalomyelitis/chronic fatigue syndrome: monocytic dysregulation and drug repurposing |
| title_sort | exploring the shared mechanism of fatigue between systemic lupus erythematosus and myalgic encephalomyelitis chronic fatigue syndrome monocytic dysregulation and drug repurposing |
| topic | systemic lupus erythematosus myalgic encephalomyelitis/chronic fatigue syndrome fatigue bioinformatics analysis single-cell transcriptomics |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1440922/full |
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