TSPO Deficiency Exacerbates GSDMD-Mediated Macrophage Pyroptosis in Inflammatory Bowel Disease
Xue Zhang,
Jingyi Han,
Yi Xu,
Menghua Cai,
Fei Gao,
Jiajia Han,
Dongdong Wang,
Yi Fu,
Hui Chen,
Wei He,
Jianmin Zhang
Affiliations
Xue Zhang
Department of Immunology, Research Center on Pediatric Development and Diseases, Chinese Academy of Medical Sciences, Key Laboratory of T Cell and Cancer Immunotherapy, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, State Key Laboratory of Medical Molecular Biology, Beijing 100005, China
Jingyi Han
Department of Immunology, Research Center on Pediatric Development and Diseases, Chinese Academy of Medical Sciences, Key Laboratory of T Cell and Cancer Immunotherapy, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, State Key Laboratory of Medical Molecular Biology, Beijing 100005, China
Yi Xu
Department of Immunology, Research Center on Pediatric Development and Diseases, Chinese Academy of Medical Sciences, Key Laboratory of T Cell and Cancer Immunotherapy, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, State Key Laboratory of Medical Molecular Biology, Beijing 100005, China
Menghua Cai
Department of Immunology, Research Center on Pediatric Development and Diseases, Chinese Academy of Medical Sciences, Key Laboratory of T Cell and Cancer Immunotherapy, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, State Key Laboratory of Medical Molecular Biology, Beijing 100005, China
Fei Gao
Department of Immunology, Research Center on Pediatric Development and Diseases, Chinese Academy of Medical Sciences, Key Laboratory of T Cell and Cancer Immunotherapy, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, State Key Laboratory of Medical Molecular Biology, Beijing 100005, China
Jiajia Han
Department of Immunology, Research Center on Pediatric Development and Diseases, Chinese Academy of Medical Sciences, Key Laboratory of T Cell and Cancer Immunotherapy, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, State Key Laboratory of Medical Molecular Biology, Beijing 100005, China
Dongdong Wang
Department of Immunology, Research Center on Pediatric Development and Diseases, Chinese Academy of Medical Sciences, Key Laboratory of T Cell and Cancer Immunotherapy, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, State Key Laboratory of Medical Molecular Biology, Beijing 100005, China
Yi Fu
Department of Immunology, Research Center on Pediatric Development and Diseases, Chinese Academy of Medical Sciences, Key Laboratory of T Cell and Cancer Immunotherapy, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, State Key Laboratory of Medical Molecular Biology, Beijing 100005, China
Hui Chen
Department of Immunology, Research Center on Pediatric Development and Diseases, Chinese Academy of Medical Sciences, Key Laboratory of T Cell and Cancer Immunotherapy, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, State Key Laboratory of Medical Molecular Biology, Beijing 100005, China
Wei He
Department of Immunology, Research Center on Pediatric Development and Diseases, Chinese Academy of Medical Sciences, Key Laboratory of T Cell and Cancer Immunotherapy, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, State Key Laboratory of Medical Molecular Biology, Beijing 100005, China
Jianmin Zhang
Department of Immunology, Research Center on Pediatric Development and Diseases, Chinese Academy of Medical Sciences, Key Laboratory of T Cell and Cancer Immunotherapy, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, State Key Laboratory of Medical Molecular Biology, Beijing 100005, China
Background: the 18-kDa translocator protein (TSPO) is a mitochondrial outer membrane protein, and its expression tends to increase in response to inflammatory stimulation, rapidly. However, the role of TSPO in inflammation and pyroptosis is not yet clear. Here, we identified TSPO as a novel key regulator of pyroptosis. (2) Methods: TSPO knockout and DSS induced mouse inflammatory bowel disease (IBD) models were employed to assess the roles of TSPO in the pathogenesis of IBD. Primary peritoneal macrophages from TSPO knockout mice were applied to evaluate the mechanism of TSPO in cell pyroptosis. Conclusions: in response to inflammatory injury, TSPO expression is rapidly upregulated and provides a protective function against GSDMD-mediated pyroptosis, which helps us better understand the biological role of TSPO and a novel regulatory mechanism of the pyroptosis process.
