Frontiers in Immunology (Feb 2021)
TGR5 Regulates Macrophage Inflammation in Nonalcoholic Steatohepatitis by Modulating NLRP3 Inflammasome Activation
- Yong Shi,
- Yong Shi,
- Yong Shi,
- Yong Shi,
- Yong Shi,
- Wantong Su,
- Wantong Su,
- Wantong Su,
- Wantong Su,
- Wantong Su,
- Lei Zhang,
- Lei Zhang,
- Lei Zhang,
- Lei Zhang,
- Lei Zhang,
- Chengyu Shi,
- Chengyu Shi,
- Chengyu Shi,
- Chengyu Shi,
- Chengyu Shi,
- Jinren Zhou,
- Jinren Zhou,
- Jinren Zhou,
- Jinren Zhou,
- Jinren Zhou,
- Peng Wang,
- Peng Wang,
- Peng Wang,
- Peng Wang,
- Peng Wang,
- Hao Wang,
- Hao Wang,
- Hao Wang,
- Hao Wang,
- Hao Wang,
- Xiaoli Shi,
- Xiaoli Shi,
- Xiaoli Shi,
- Xiaoli Shi,
- Xiaoli Shi,
- Song Wei,
- Song Wei,
- Song Wei,
- Song Wei,
- Song Wei,
- Qi Wang,
- Qi Wang,
- Qi Wang,
- Qi Wang,
- Qi Wang,
- Johan Auwerx,
- Kristina Schoonjans,
- Yue Yu,
- Yue Yu,
- Yue Yu,
- Yue Yu,
- Yue Yu,
- Rui Pan,
- Haoming Zhou,
- Haoming Zhou,
- Haoming Zhou,
- Haoming Zhou,
- Haoming Zhou,
- Ling Lu,
- Ling Lu,
- Ling Lu,
- Ling Lu,
- Ling Lu
Affiliations
- Yong Shi
- Jiangsu Key Laboratory of Molecular and Translational Cancer Research, The Affiliated Cancer Hospital (Jiangsu Cancer Hospital), Nanjing Medical University, Nanjing, China
- Yong Shi
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University & Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences, Nanjing, China
- Yong Shi
- State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China
- Yong Shi
- Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, College of Chemistry and Materials Science, Nanjing Normal University, Nanjing, China
- Yong Shi
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University, Nanjing, China
- Wantong Su
- Jiangsu Key Laboratory of Molecular and Translational Cancer Research, The Affiliated Cancer Hospital (Jiangsu Cancer Hospital), Nanjing Medical University, Nanjing, China
- Wantong Su
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University & Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences, Nanjing, China
- Wantong Su
- State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China
- Wantong Su
- Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, College of Chemistry and Materials Science, Nanjing Normal University, Nanjing, China
- Wantong Su
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University, Nanjing, China
- Lei Zhang
- Jiangsu Key Laboratory of Molecular and Translational Cancer Research, The Affiliated Cancer Hospital (Jiangsu Cancer Hospital), Nanjing Medical University, Nanjing, China
- Lei Zhang
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University & Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences, Nanjing, China
- Lei Zhang
- State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China
- Lei Zhang
- Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, College of Chemistry and Materials Science, Nanjing Normal University, Nanjing, China
- Lei Zhang
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University, Nanjing, China
- Chengyu Shi
- Jiangsu Key Laboratory of Molecular and Translational Cancer Research, The Affiliated Cancer Hospital (Jiangsu Cancer Hospital), Nanjing Medical University, Nanjing, China
- Chengyu Shi
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University & Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences, Nanjing, China
- Chengyu Shi
- State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China
- Chengyu Shi
- Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, College of Chemistry and Materials Science, Nanjing Normal University, Nanjing, China
- Chengyu Shi
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University, Nanjing, China
- Jinren Zhou
- Jiangsu Key Laboratory of Molecular and Translational Cancer Research, The Affiliated Cancer Hospital (Jiangsu Cancer Hospital), Nanjing Medical University, Nanjing, China
- Jinren Zhou
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University & Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences, Nanjing, China
- Jinren Zhou
- State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China
- Jinren Zhou
- Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, College of Chemistry and Materials Science, Nanjing Normal University, Nanjing, China
- Jinren Zhou
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University, Nanjing, China
- Peng Wang
- Jiangsu Key Laboratory of Molecular and Translational Cancer Research, The Affiliated Cancer Hospital (Jiangsu Cancer Hospital), Nanjing Medical University, Nanjing, China
- Peng Wang
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University & Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences, Nanjing, China
- Peng Wang
- State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China
- Peng Wang
- Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, College of Chemistry and Materials Science, Nanjing Normal University, Nanjing, China
- Peng Wang
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University, Nanjing, China
- Hao Wang
- Jiangsu Key Laboratory of Molecular and Translational Cancer Research, The Affiliated Cancer Hospital (Jiangsu Cancer Hospital), Nanjing Medical University, Nanjing, China
- Hao Wang
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University & Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences, Nanjing, China
- Hao Wang
- State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China
- Hao Wang
- Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, College of Chemistry and Materials Science, Nanjing Normal University, Nanjing, China
- Hao Wang
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University, Nanjing, China
- Xiaoli Shi
- Jiangsu Key Laboratory of Molecular and Translational Cancer Research, The Affiliated Cancer Hospital (Jiangsu Cancer Hospital), Nanjing Medical University, Nanjing, China
- Xiaoli Shi
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University & Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences, Nanjing, China
- Xiaoli Shi
- State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China
- Xiaoli Shi
- Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, College of Chemistry and Materials Science, Nanjing Normal University, Nanjing, China
- Xiaoli Shi
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University, Nanjing, China
- Song Wei
- Jiangsu Key Laboratory of Molecular and Translational Cancer Research, The Affiliated Cancer Hospital (Jiangsu Cancer Hospital), Nanjing Medical University, Nanjing, China
- Song Wei
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University & Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences, Nanjing, China
- Song Wei
- State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China
- Song Wei
- Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, College of Chemistry and Materials Science, Nanjing Normal University, Nanjing, China
- Song Wei
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University, Nanjing, China
- Qi Wang
- Jiangsu Key Laboratory of Molecular and Translational Cancer Research, The Affiliated Cancer Hospital (Jiangsu Cancer Hospital), Nanjing Medical University, Nanjing, China
- Qi Wang
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University & Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences, Nanjing, China
- Qi Wang
- State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China
- Qi Wang
- Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, College of Chemistry and Materials Science, Nanjing Normal University, Nanjing, China
- Qi Wang
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University, Nanjing, China
- Johan Auwerx
- Metabolic Signaling, School of Life Sciences, Institute of Bioengineering, Ecole Polytechnique Federale de Lausanne, Lausanne, Switzerland
- Kristina Schoonjans
- Metabolic Signaling, School of Life Sciences, Institute of Bioengineering, Ecole Polytechnique Federale de Lausanne, Lausanne, Switzerland
- Yue Yu
- Jiangsu Key Laboratory of Molecular and Translational Cancer Research, The Affiliated Cancer Hospital (Jiangsu Cancer Hospital), Nanjing Medical University, Nanjing, China
- Yue Yu
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University & Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences, Nanjing, China
- Yue Yu
- State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China
- Yue Yu
- Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, College of Chemistry and Materials Science, Nanjing Normal University, Nanjing, China
- Yue Yu
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University, Nanjing, China
- Rui Pan
- Jiangsu Key Laboratory of Molecular and Translational Cancer Research, The Affiliated Cancer Hospital (Jiangsu Cancer Hospital), Nanjing Medical University, Nanjing, China
- Haoming Zhou
- Jiangsu Key Laboratory of Molecular and Translational Cancer Research, The Affiliated Cancer Hospital (Jiangsu Cancer Hospital), Nanjing Medical University, Nanjing, China
- Haoming Zhou
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University & Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences, Nanjing, China
- Haoming Zhou
- State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China
- Haoming Zhou
- Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, College of Chemistry and Materials Science, Nanjing Normal University, Nanjing, China
- Haoming Zhou
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University, Nanjing, China
- Ling Lu
- Jiangsu Key Laboratory of Molecular and Translational Cancer Research, The Affiliated Cancer Hospital (Jiangsu Cancer Hospital), Nanjing Medical University, Nanjing, China
- Ling Lu
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University & Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences, Nanjing, China
- Ling Lu
- State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China
- Ling Lu
- Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, College of Chemistry and Materials Science, Nanjing Normal University, Nanjing, China
- Ling Lu
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University, Nanjing, China
- DOI
- https://doi.org/10.3389/fimmu.2020.609060
- Journal volume & issue
-
Vol. 11
Abstract
Nonalcoholic steatohepatitis (NASH) is a chronic liver disease associated with dysregulation of liver metabolism and inflammation. G-protein coupled bile acid receptor 1 (TGR5) is a cell surface receptor that is involved in multiple metabolic pathways. However, the functions of TGR5 in regulating macrophage innate immune activation in NASH remain unclear. Here, we found that TGR5 expression was decreased in liver tissues from humans and mice with NASH. Compared to wild type (WT) mice, TGR5-knockout (TGR5−/−) mice exhibited exacerbated liver damage, increased levels of proinflammatory factors, and enhanced M1 macrophage polarization. Moreover, TGR5 deficiency facilitated M1 macrophage polarization by promoting NLRP3 inflammasome activation and caspase-1 cleavage. Taken together, our findings revealed that TGR5 signaling attenuated liver steatosis and inflammation and inhibited NLRP3-mediated M1 macrophage polarization in NASH.
Keywords
- nonalcoholic steatohepatitis
- G protein-coupled bile acid receptor 1
- macrophages
- inflammation
- NLRP3 inflammasome
