title: Natural killer T cells play a necessary role in modulating of immune-mediated liver injury by gut microbiota.
abstract: Gut microbiota are implicated in many liver diseases. Concanavalin A (ConA)-induced hepatitis is a well-characterized murine model of fulminant immunological hepatic injury. Oral administration of pathogenic bacteria or gentamycin to the mice before ConA injection, liver injury and lymphocyte distribution in liver and intestine were assessed. Our data show that administration of pathogenic bacteria exacerbated the liver damage. There was more downregulation of activation-induced natural killer T (NKT) cells in the liver of pathogenic bacteria-treated ConA groups. Also, there was a negative correlation between the numbers of hepatic NKT cells and liver injury in our experiments. Moreover, intestinal dendritic cells (DCs) were increased in pathogenic bacteria-treated ConA groups. The activation of DCs in Peyer's patches and the liver was similar to the intestine. However, depletion of gut gram-negative bacteria alleviated ConA-induced liver injury, through suppressed hepatic NKT cells activation and DCs homing in liver and intestine. In vitro experiments revealed that DCs promoted NKT cell cytotoxicity against hepatocyte following stimulation with pathogenic bacteria. Our study suggests that increased intestinal pathogenic bacteria facilitate immune-mediated liver injury, which may be due to the activation of NKT cells that mediated by intestinal bacterial antigens activated DCs.
authors.affiliation: 1] State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China [2] Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors.forename: Jianing
authors.initials: J
authors.lastname: Chen
authors.affiliation: 1] State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China [2] Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors.forename: Yingfeng
authors.initials: Y
authors.lastname: Wei
authors.affiliation: 1] State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China [2] Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors.forename: Jianqin
authors.initials: J
authors.lastname: He
authors.affiliation: 1] State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China [2] Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors.forename: Guangying
authors.initials: G
authors.lastname: Cui
authors.affiliation: 1] State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China [2] Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors.forename: Yunan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: 1] State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China [2] Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Lu
authors.affiliation: 1] State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China [2] Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Ding
authors.affiliation: 1] Institute of Immunology and Key Laboratory of Innate Immunity and Chronic Disease of CAS, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei 230027, China [2] Innovation Center for Cell Biology, Hefei National Laboratory for Physical Sciences at Microscale, Hefei 230027, China.
authors.forename: Rufeng
authors.initials: R
authors.lastname: Xue
authors.affiliation: 1] Institute of Immunology and Key Laboratory of Innate Immunity and Chronic Disease of CAS, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei 230027, China [2] Innovation Center for Cell Biology, Hefei National Laboratory for Physical Sciences at Microscale, Hefei 230027, China.
authors.forename: Li
authors.initials: L
authors.lastname: Bai
authors.affiliation: Molecular Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo, 0600815, Japan.
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Uede
authors.affiliation: 1] State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China [2] Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors.forename: Lanjuan
authors.initials: L
authors.lastname: Li
authors.affiliation: 1] State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China [2] Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Diao
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology; D005260:Female; D006505:Hepatitis / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D056747:Immunomodulation / Q000276:immunology; D007422:Intestines / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota / Q000276:immunology*; D018448:Models, Immunological; D055611:Natural Killer T-Cells / Q000276:immunology*; D019936:Probiotics / Q000627:therapeutic use*; D016896:Treatment Outcome