title: Gut-derived lymphocyte recruitment to liver and induce liver injury in non-alcoholic fatty liver disease mouse model.
abstract: OBJECTIVE
  Most studies focus on gut-derived factors like microbiota and its products and how they contribute to non-alcoholic fatty liver disease (NAFLD) progression. This study investigated whether the gut-derived lymphocytes could migrate to the liver and induce liver injury in NAFLD.
  
  
  METHODS
  A high-fat diet induced an NAFLD mouse model, and lymphocytes were labeled with 1,1-dioctadecyl-3,3,3,3 tetramethylindotricarbocyanine iodide and carboxy-fluorescein succinimidyl ester, respectively, and intravenously injected to mice to monitor lymphocyte migration.
  
  
  RESULTS
  Adoptive transfer model results indicated that compared with lymphocytes from the spleen, bone marrow and thymus of NAFLD donor mice, mesenteric lymph nodes (MLN) cells from NAFLD donor mice predominately accumulated in the livers of NAFLD recipient mice. The frequencies of central memory CD4(+) T and CD8(+) T cells in livers of NAFLD mice were significantly increased; however, the activated T cells were not significantly altered. After adoptively transferred MLN cells, the frequencies of the activated CD4(+) T and CD8(+) T cells increased in livers of NAFLD recipient mice. By contrast, the frequencies of central memory and naïve CD4(+) T and CD8(+) T cells decreased. MLN cells also induced liver injury in NAFLD recipient mice, as reflected by elevated serum alanine aminotransferase and glutamic oxaloacetic transaminase serums. Moreover, the chemotaxis assay showed that CCL5 mediated the MLN cell migration to the liver. Also, blocking the CCL5 inhibited MLN cell migration to the liver in vitro.
  
  
  CONCLUSIONS
  Gut-derived lymphocytes from NAFLD mice could migrate to the liver and induce liver injury and hepatic CD4(+) T and CD8(+) T cells activation. The migration was associated with the upregulation of CCL5 in the liver.
authors.affiliation: Department of Gastroenterology, Peking University People's Hospital, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Peking University Hepatology Institute, Peking University People's Hospital, Beijing, China.
authors.forename: Henghui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Peking University People's Hospital, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Peking University Hepatology Institute, Peking University People's Hospital, Beijing, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Cong
authors.affiliation: Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Peking University Hepatology Institute, Peking University People's Hospital, Beijing, China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Peking University Hepatology Institute, Peking University People's Hospital, Beijing, China.
authors.forename: Gaixia
authors.initials: G
authors.lastname: He
authors.affiliation: Institute of Clinical Molecular Biology, Peking University People's Hospital, Beijing, China.
authors.forename: Yujing
authors.initials: Y
authors.lastname: Chi
authors.affiliation: Department of Gastroenterology, Peking University People's Hospital, Beijing, China.
authors.forename: Yulan
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D002465:Cell Movement; D018946:Chemokine CCL5 / Q000502:physiology; D004195:Disease Models, Animal; D008099:Liver / Q000166:cytology* / Q000473:pathology*; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000473:pathology*; D008297:Male; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000473:pathology*; D015854:Up-Regulation
chemical_list: D018946:Chemokine CCL5
keywords: gut; lymphocyte; migration; non-alcoholic fatty liver disease.