Microbiota‐Derived Inosine Suppresses Systemic Autoimmunity via Restriction of B Cell Differentiation and Migration
Abstract The role of gut microbiota dysbiosis in systemic lupus erythematosus (SLE) pathogenesis remains elusive. Here, it is shown that fecal microbiota transplantation (FMT) from healthy mice to lupus mice ameliorates lupus‐like symptoms. Microbiota reconstitution effectively reduces systemic clas...
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| Format: | Article |
| Language: | English |
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Wiley
2025-05-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202409837 |
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| author | Lingyu Gao Yuhan Zhang Zhi Hu Shengwen Chen Qiaolin Wang Yong Zeng Huiqi Yin Junpeng Zhao Yijing Zhan Changxing Gao Yue Xin Bing Chen Stijn van derVeen Ming Zhao Deyu Fang Qianjin Lu |
| author_facet | Lingyu Gao Yuhan Zhang Zhi Hu Shengwen Chen Qiaolin Wang Yong Zeng Huiqi Yin Junpeng Zhao Yijing Zhan Changxing Gao Yue Xin Bing Chen Stijn van derVeen Ming Zhao Deyu Fang Qianjin Lu |
| author_sort | Lingyu Gao |
| collection | DOAJ |
| description | Abstract The role of gut microbiota dysbiosis in systemic lupus erythematosus (SLE) pathogenesis remains elusive. Here, it is shown that fecal microbiota transplantation (FMT) from healthy mice to lupus mice ameliorates lupus‐like symptoms. Microbiota reconstitution effectively reduces systemic class switch recombination (CSR) and elevates immunoglobulin heavy chain (IGH) naïve isotype. Microbiota profiling reveals an enrichment of Lactobacillus johnsonii post‐FMT, with a significant correlation to purine metabolites. Importantly, the L. johnsonii‐derived inosine, an intermediate metabolite in purine metabolism, effectively alleviates lupus pathogenesis in mice. Inosine inhibits B cell differentiation and reduces renal B cell infiltration to protect mice from lupus. At the molecular level, inosine reprograms B cells through the extracellular signal‐regulated kinase (ERK)‐hypoxia‐inducible factor‐1alpha (HIF‐1α) signaling pathway. Therefore, this study highlights the discovery of a novel microbial metabolite modulating autoimmunity and suggests its potential for innovative microbiome‐based therapeutic approaches. |
| format | Article |
| id | doaj-art-0bc4649966c04a15bb60ee1ae301f39e |
| institution | OA Journals |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-0bc4649966c04a15bb60ee1ae301f39e2025-08-20T02:34:43ZengWileyAdvanced Science2198-38442025-05-011220n/an/a10.1002/advs.202409837Microbiota‐Derived Inosine Suppresses Systemic Autoimmunity via Restriction of B Cell Differentiation and MigrationLingyu Gao0Yuhan Zhang1Zhi Hu2Shengwen Chen3Qiaolin Wang4Yong Zeng5Huiqi Yin6Junpeng Zhao7Yijing Zhan8Changxing Gao9Yue Xin10Bing Chen11Stijn van derVeen12Ming Zhao13Deyu Fang14Qianjin Lu15Hospital for Skin Diseases Institute of Dermatology Chinese Academy of Medical Sciences and Peking Union Medical College Nanjing 210042 ChinaHospital for Skin Diseases Institute of Dermatology Chinese Academy of Medical Sciences and Peking Union Medical College Nanjing 210042 ChinaHospital for Skin Diseases Institute of Dermatology Chinese Academy of Medical Sciences and Peking Union Medical College Nanjing 210042 ChinaHospital for Skin Diseases Institute of Dermatology Chinese Academy of Medical Sciences and Peking Union Medical College Nanjing 210042 ChinaHospital for Skin Diseases Institute of Dermatology Chinese Academy of Medical Sciences and Peking Union Medical College Nanjing 210042 ChinaHunan Key Laboratory of Medical Epigenomics The Second Xiangya Hospital Central South University Changsha 410013 ChinaHospital for Skin Diseases Institute of Dermatology Chinese Academy of Medical Sciences and Peking Union Medical College Nanjing 210042 ChinaHospital for Skin Diseases Institute of Dermatology Chinese Academy of Medical Sciences and Peking Union Medical College Nanjing 210042 ChinaHospital for Skin Diseases Institute of Dermatology Chinese Academy of Medical Sciences and Peking Union Medical College Nanjing 210042 ChinaHospital for Skin Diseases Institute of Dermatology Chinese Academy of Medical Sciences and Peking Union Medical College Nanjing 210042 ChinaHospital for Skin Diseases Institute of Dermatology Chinese Academy of Medical Sciences and Peking Union Medical College Nanjing 210042 ChinaClinical Laboratory The Second Hospital of Anhui Medical University Hefei 230601 ChinaDepartment of Microbiology and Department of Dermatology Sir Run Run Shaw Hospital School of Medicine Zhejiang University Hangzhou 310058 ChinaHospital for Skin Diseases Institute of Dermatology Chinese Academy of Medical Sciences and Peking Union Medical College Nanjing 210042 ChinaDepartment of Pathology Northwestern University Feinberg School of Medicine Chicago IL 60611 USAHospital for Skin Diseases Institute of Dermatology Chinese Academy of Medical Sciences and Peking Union Medical College Nanjing 210042 ChinaAbstract The role of gut microbiota dysbiosis in systemic lupus erythematosus (SLE) pathogenesis remains elusive. Here, it is shown that fecal microbiota transplantation (FMT) from healthy mice to lupus mice ameliorates lupus‐like symptoms. Microbiota reconstitution effectively reduces systemic class switch recombination (CSR) and elevates immunoglobulin heavy chain (IGH) naïve isotype. Microbiota profiling reveals an enrichment of Lactobacillus johnsonii post‐FMT, with a significant correlation to purine metabolites. Importantly, the L. johnsonii‐derived inosine, an intermediate metabolite in purine metabolism, effectively alleviates lupus pathogenesis in mice. Inosine inhibits B cell differentiation and reduces renal B cell infiltration to protect mice from lupus. At the molecular level, inosine reprograms B cells through the extracellular signal‐regulated kinase (ERK)‐hypoxia‐inducible factor‐1alpha (HIF‐1α) signaling pathway. Therefore, this study highlights the discovery of a novel microbial metabolite modulating autoimmunity and suggests its potential for innovative microbiome‐based therapeutic approaches.https://doi.org/10.1002/advs.202409837systemic lupus erythematosus (SLE)lupus nephritis (LN)fecal microbiota transplantation (FMT)Lactobacillus johnsoniipurine metabolitesinosine |
| spellingShingle | Lingyu Gao Yuhan Zhang Zhi Hu Shengwen Chen Qiaolin Wang Yong Zeng Huiqi Yin Junpeng Zhao Yijing Zhan Changxing Gao Yue Xin Bing Chen Stijn van derVeen Ming Zhao Deyu Fang Qianjin Lu Microbiota‐Derived Inosine Suppresses Systemic Autoimmunity via Restriction of B Cell Differentiation and Migration Advanced Science systemic lupus erythematosus (SLE) lupus nephritis (LN) fecal microbiota transplantation (FMT) Lactobacillus johnsonii purine metabolites inosine |
| title | Microbiota‐Derived Inosine Suppresses Systemic Autoimmunity via Restriction of B Cell Differentiation and Migration |
| title_full | Microbiota‐Derived Inosine Suppresses Systemic Autoimmunity via Restriction of B Cell Differentiation and Migration |
| title_fullStr | Microbiota‐Derived Inosine Suppresses Systemic Autoimmunity via Restriction of B Cell Differentiation and Migration |
| title_full_unstemmed | Microbiota‐Derived Inosine Suppresses Systemic Autoimmunity via Restriction of B Cell Differentiation and Migration |
| title_short | Microbiota‐Derived Inosine Suppresses Systemic Autoimmunity via Restriction of B Cell Differentiation and Migration |
| title_sort | microbiota derived inosine suppresses systemic autoimmunity via restriction of b cell differentiation and migration |
| topic | systemic lupus erythematosus (SLE) lupus nephritis (LN) fecal microbiota transplantation (FMT) Lactobacillus johnsonii purine metabolites inosine |
| url | https://doi.org/10.1002/advs.202409837 |
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