title: The microbiota maintain homeostasis of liver-resident γδT-17 cells in a lipid antigen/CD1d-dependent manner.
abstract: The microbiota control regional immunity using mechanisms such as inducing IL-17A-producing γδ T (γδT-17) cells in various tissues. However, little is known regarding hepatic γδT cells that are constantly stimulated by gut commensal microbes. Here we show hepatic γδT cells are liver-resident cells and predominant producers of IL-17A. The microbiota sustain hepatic γδT-17 cell homeostasis, including activation, survival and proliferation. The global commensal quantity affects the number of liver-resident γδT-17 cells; indeed, E. coli alone can generate γδT-17 cells in a dose-dependent manner. Liver-resident γδT-17 cell homeostasis depends on hepatocyte-expressed CD1d, that present lipid antigen, but not Toll-like receptors or IL-1/IL-23 receptor signalling. Supplementing mice in vivo or loading hepatocytes in vitro with exogenous commensal lipid antigens augments the hepatic γδT-17 cell number. Moreover, the microbiota accelerate nonalcoholic fatty liver disease through hepatic γδT-17 cells. Thus, our work describes a unique liver-resident γδT-17 cell subset maintained by gut commensal microbes through CD1d/lipid antigens.
authors.affiliation: Institute of Immunology and the Key Laboratory of Innate Immunity and Chronic Disease (Chinese Academy of Science), School of Life Science and Medical Center, University of Science and Technology of China, Hefei 230027, China.
authors.forename: Fenglei
authors.initials: F
authors.lastname: Li
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Hao
authors.affiliation: Institute of Immunology and the Key Laboratory of Innate Immunity and Chronic Disease (Chinese Academy of Science), School of Life Science and Medical Center, University of Science and Technology of China, Hefei 230027, China.
authors.forename: Yongyan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Institute of Immunology and the Key Laboratory of Innate Immunity and Chronic Disease (Chinese Academy of Science), School of Life Science and Medical Center, University of Science and Technology of China, Hefei 230027, China.
authors.forename: Li
authors.initials: L
authors.lastname: Bai
authors.affiliation: Model Animal Research Center, Nanjing University, Nanjing, Jiangsu 210061, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.affiliation: Institute of Immunology and the Key Laboratory of Innate Immunity and Chronic Disease (Chinese Academy of Science), School of Life Science and Medical Center, University of Science and Technology of China, Hefei 230027, China.
authors.forename: Zhexiong
authors.initials: Z
authors.lastname: Lian
authors.affiliation: Institute of Immunology and the Key Laboratory of Innate Immunity and Chronic Disease (Chinese Academy of Science), School of Life Science and Medical Center, University of Science and Technology of China, Hefei 230027, China.|Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, China.
authors.forename: Haiming
authors.initials: H
authors.lastname: Wei
authors.affiliation: Institute of Immunology and the Key Laboratory of Innate Immunity and Chronic Disease (Chinese Academy of Science), School of Life Science and Medical Center, University of Science and Technology of China, Hefei 230027, China.|Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, China.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Sun
authors.affiliation: Institute of Immunology and the Key Laboratory of Innate Immunity and Chronic Disease (Chinese Academy of Science), School of Life Science and Medical Center, University of Science and Technology of China, Hefei 230027, China.|Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, China.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Tian
mesh_terms: D000818:Animals; D055610:Antigens, CD1d / Q000378:metabolism*; D002478:Cells, Cultured; D004926:Escherichia coli / Q000276:immunology; D000069196:Gastrointestinal Microbiome / Q000276:immunology*; D022781:Hepatocytes / Q000276:immunology; D020381:Interleukin-17 / Q000096:biosynthesis; D008099:Liver / Q000166:cytology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D065626:Non-alcoholic Fatty Liver Disease / Q000276:immunology / Q000473:pathology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D055610:Antigens, CD1d; C584692:CD1d antigen, mouse; C098680:Il17a protein, mouse; D020381:Interleukin-17; D016692:Receptors, Antigen, T-Cell, gamma-delta