RNF128 deficiency in macrophages promotes colonic inflammation by suppressing the autophagic degradation of S100A8
Abstract Macrophages play important roles in maintaining intestinal homeostasis and in the pathogenesis of inflammatory bowel diseases (IBDs). However, the underlying mechanisms that govern macrophage-mediated inflammation are still largely unknown. In this study, we report that RNF128 is downregula...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-01-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-025-07338-0 |
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| _version_ | 1832594442255597568 |
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| author | Xianwen Ran Yue Li Yahui Ren Weilong Chang Rui Deng Huifen Wang Weiwei Zhu Yize Zhang Yudie Cai Jia Hu Di Wang Zhibo Liu |
| author_facet | Xianwen Ran Yue Li Yahui Ren Weilong Chang Rui Deng Huifen Wang Weiwei Zhu Yize Zhang Yudie Cai Jia Hu Di Wang Zhibo Liu |
| author_sort | Xianwen Ran |
| collection | DOAJ |
| description | Abstract Macrophages play important roles in maintaining intestinal homeostasis and in the pathogenesis of inflammatory bowel diseases (IBDs). However, the underlying mechanisms that govern macrophage-mediated inflammation are still largely unknown. In this study, we report that RNF128 is downregulated in proinflammatory macrophages. RNF128 deficiency leads to elevated levels of effector cytokines in vitro and accelerates the progression of IBD in mouse models. Bone marrow transplantation experiments revealed that RNF128 deficiency in bone marrow cells contributes to the worsening of DSS-induced colitis. Mechanistically, RNF128 interacts with and destabilizes S100A8 by promoting its autophagic degradation, which is mediated by the cargo receptor Tollip. Moreover, the administration of an S100A8 neutralizing antibody mitigated the development of colitis and improved survival in DSS-treated Rnf128 −/− mice. Overall, our study underscores the anti-inflammatory role of RNF128 in macrophages during the progression of colitis and highlights the potential of targeting the RNF128-Tollip-S100A8 axis to attenuate intestinal inflammation for the treatment of colitis. |
| format | Article |
| id | doaj-art-d2d21c81558d4175b7ef5c673b5cd755 |
| institution | Kabale University |
| issn | 2041-4889 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj-art-d2d21c81558d4175b7ef5c673b5cd7552025-01-19T12:40:46ZengNature Publishing GroupCell Death and Disease2041-48892025-01-0116111410.1038/s41419-025-07338-0RNF128 deficiency in macrophages promotes colonic inflammation by suppressing the autophagic degradation of S100A8Xianwen Ran0Yue Li1Yahui Ren2Weilong Chang3Rui Deng4Huifen Wang5Weiwei Zhu6Yize Zhang7Yudie Cai8Jia Hu9Di Wang10Zhibo Liu11Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou UniversityTranslational Medicine Center, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Infectious Diseases, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Infectious Diseases, The First Affiliated Hospital of Zhengzhou UniversityGene Hospital of Henan Province, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Infectious Diseases, The First Affiliated Hospital of Zhengzhou UniversityInstitute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and TechnologyDepartment of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou UniversityAbstract Macrophages play important roles in maintaining intestinal homeostasis and in the pathogenesis of inflammatory bowel diseases (IBDs). However, the underlying mechanisms that govern macrophage-mediated inflammation are still largely unknown. In this study, we report that RNF128 is downregulated in proinflammatory macrophages. RNF128 deficiency leads to elevated levels of effector cytokines in vitro and accelerates the progression of IBD in mouse models. Bone marrow transplantation experiments revealed that RNF128 deficiency in bone marrow cells contributes to the worsening of DSS-induced colitis. Mechanistically, RNF128 interacts with and destabilizes S100A8 by promoting its autophagic degradation, which is mediated by the cargo receptor Tollip. Moreover, the administration of an S100A8 neutralizing antibody mitigated the development of colitis and improved survival in DSS-treated Rnf128 −/− mice. Overall, our study underscores the anti-inflammatory role of RNF128 in macrophages during the progression of colitis and highlights the potential of targeting the RNF128-Tollip-S100A8 axis to attenuate intestinal inflammation for the treatment of colitis.https://doi.org/10.1038/s41419-025-07338-0 |
| spellingShingle | Xianwen Ran Yue Li Yahui Ren Weilong Chang Rui Deng Huifen Wang Weiwei Zhu Yize Zhang Yudie Cai Jia Hu Di Wang Zhibo Liu RNF128 deficiency in macrophages promotes colonic inflammation by suppressing the autophagic degradation of S100A8 Cell Death and Disease |
| title | RNF128 deficiency in macrophages promotes colonic inflammation by suppressing the autophagic degradation of S100A8 |
| title_full | RNF128 deficiency in macrophages promotes colonic inflammation by suppressing the autophagic degradation of S100A8 |
| title_fullStr | RNF128 deficiency in macrophages promotes colonic inflammation by suppressing the autophagic degradation of S100A8 |
| title_full_unstemmed | RNF128 deficiency in macrophages promotes colonic inflammation by suppressing the autophagic degradation of S100A8 |
| title_short | RNF128 deficiency in macrophages promotes colonic inflammation by suppressing the autophagic degradation of S100A8 |
| title_sort | rnf128 deficiency in macrophages promotes colonic inflammation by suppressing the autophagic degradation of s100a8 |
| url | https://doi.org/10.1038/s41419-025-07338-0 |
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