Targeting immune cellular populations and transcription factors: unraveling the therapeutic potential of JQF for NAFLD
BackgroundNon-alcoholic fatty liver disease (NAFLD) constitutes the most prevalent chronic liver disease worldwide. Progression to non-alcoholic steatohepatitis (NASH), the immune cell reservoir within the liver undergoes remodeling, exacerbating liver inflammation and potentially leading to liver f...
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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.2024.1445924/full |
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| author | Lijuan Zhou Jingyi Zhao Kaile Ma Rui Hao Chensi Yao Xiaowen Gou Chuanxi Tian Li Wan Min Li Xiaolin Tong |
| author_facet | Lijuan Zhou Jingyi Zhao Kaile Ma Rui Hao Chensi Yao Xiaowen Gou Chuanxi Tian Li Wan Min Li Xiaolin Tong |
| author_sort | Lijuan Zhou |
| collection | DOAJ |
| description | BackgroundNon-alcoholic fatty liver disease (NAFLD) constitutes the most prevalent chronic liver disease worldwide. Progression to non-alcoholic steatohepatitis (NASH), the immune cell reservoir within the liver undergoes remodeling, exacerbating liver inflammation and potentially leading to liver fibrosis. Jiangtang Qingre Formula (JQF) is an effective prescription for the clinical treatment of NAFLD. However, its underlying mechanism of action remains unclear.MethodsUsing a high-fat diet-induced NAFLD mouse model, we evaluated JQF’s effects with biochemical tests and histopathology. Single-cell RNA sequencing and spatial transcriptomics furthered our understanding of NAFLD pathophysiology and JQF’s treatment mechanisms.ResultsOur findings initially revealed significant improvements in JQF on hepatic steatosis, inflammation, fibrosis and glucose tolerance in NAFLD mice. Furthermore, significant changes were observed in the immune cells including monocytes, macrophages, and T cells in the livers of NAFLD mice. Notably, regions infiltrated by T cells presented the most severe liver inflammation and fibrosis. Importantly, JQF effectively modulated these immune cells. Advanced subcluster and cell communication analyses identified key macrophage (KCs, MoMFs) and T cell (Tc, Th2) subpopulations in JQF’s therapeutic actions. Further SCENIC analysis additionally uncovered the essential transcription factors that regulate these cell subclusters, such as Stat2, Mta3, Eomes, and Etv5.ConclusionOverall, our research suggests a promising potential therapeutic agent and identifies critical cell populations and transcription factors that contribute to its therapeutic effects, thereby revealing potential therapeutic targets for NAFLD. |
| format | Article |
| id | doaj-art-c73ebf8fcf96468db32f9bc7487529a4 |
| 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-c73ebf8fcf96468db32f9bc7487529a42025-01-07T05:24:03ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.14459241445924Targeting immune cellular populations and transcription factors: unraveling the therapeutic potential of JQF for NAFLDLijuan Zhou0Jingyi Zhao1Kaile Ma2Rui Hao3Chensi Yao4Xiaowen Gou5Chuanxi Tian6Li Wan7Min Li8Xiaolin Tong9Institute of Metabolic Diseases, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Metabolic Diseases, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Metabolic Diseases, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Metabolic Diseases, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Metabolic Diseases, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Metabolic Diseases, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaClinical Medical College, Beijing University of Chinese Medicine, Beijing, ChinaMolecular Biology Laboratory, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaMolecular Biology Laboratory, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Metabolic Diseases, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaBackgroundNon-alcoholic fatty liver disease (NAFLD) constitutes the most prevalent chronic liver disease worldwide. Progression to non-alcoholic steatohepatitis (NASH), the immune cell reservoir within the liver undergoes remodeling, exacerbating liver inflammation and potentially leading to liver fibrosis. Jiangtang Qingre Formula (JQF) is an effective prescription for the clinical treatment of NAFLD. However, its underlying mechanism of action remains unclear.MethodsUsing a high-fat diet-induced NAFLD mouse model, we evaluated JQF’s effects with biochemical tests and histopathology. Single-cell RNA sequencing and spatial transcriptomics furthered our understanding of NAFLD pathophysiology and JQF’s treatment mechanisms.ResultsOur findings initially revealed significant improvements in JQF on hepatic steatosis, inflammation, fibrosis and glucose tolerance in NAFLD mice. Furthermore, significant changes were observed in the immune cells including monocytes, macrophages, and T cells in the livers of NAFLD mice. Notably, regions infiltrated by T cells presented the most severe liver inflammation and fibrosis. Importantly, JQF effectively modulated these immune cells. Advanced subcluster and cell communication analyses identified key macrophage (KCs, MoMFs) and T cell (Tc, Th2) subpopulations in JQF’s therapeutic actions. Further SCENIC analysis additionally uncovered the essential transcription factors that regulate these cell subclusters, such as Stat2, Mta3, Eomes, and Etv5.ConclusionOverall, our research suggests a promising potential therapeutic agent and identifies critical cell populations and transcription factors that contribute to its therapeutic effects, thereby revealing potential therapeutic targets for NAFLD.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1445924/fullsingle-cell RNA sequencingspatial transcriptomicsnon-alcoholic fatty liver diseasemacrophagesT cellstraditional Chinese medicine |
| spellingShingle | Lijuan Zhou Jingyi Zhao Kaile Ma Rui Hao Chensi Yao Xiaowen Gou Chuanxi Tian Li Wan Min Li Xiaolin Tong Targeting immune cellular populations and transcription factors: unraveling the therapeutic potential of JQF for NAFLD Frontiers in Immunology single-cell RNA sequencing spatial transcriptomics non-alcoholic fatty liver disease macrophages T cells traditional Chinese medicine |
| title | Targeting immune cellular populations and transcription factors: unraveling the therapeutic potential of JQF for NAFLD |
| title_full | Targeting immune cellular populations and transcription factors: unraveling the therapeutic potential of JQF for NAFLD |
| title_fullStr | Targeting immune cellular populations and transcription factors: unraveling the therapeutic potential of JQF for NAFLD |
| title_full_unstemmed | Targeting immune cellular populations and transcription factors: unraveling the therapeutic potential of JQF for NAFLD |
| title_short | Targeting immune cellular populations and transcription factors: unraveling the therapeutic potential of JQF for NAFLD |
| title_sort | targeting immune cellular populations and transcription factors unraveling the therapeutic potential of jqf for nafld |
| topic | single-cell RNA sequencing spatial transcriptomics non-alcoholic fatty liver disease macrophages T cells traditional Chinese medicine |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1445924/full |
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