title: The roles of T helper type 17/regulatory T cells in acute rejection after liver transplantation in rats.
abstract: BACKGROUND
  Liver transplantation is a widely accepted treatment for end-stage liver disease. The aim of our study was to investigate the imbalance between T helper type 17 (Th17) and CD4(+) CD25(+) Foxp3(+) regulatory T (Treg) cells during hepatic allograft rejection in a rodent grafts model because their roles in liver transplantation is not fully understood.
  
  
  METHODS
  We compared median survival time (MST) survivals, Th17/Treg cells and related cytokines levels (interleukin [IL]-17, IL-6, IL-10, and transforming growth factor-β1), as well as serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (T-Bili) after liver transplantation. In addition, the allograft groups were injected with IL-17 neutralizing antibody to evaluate the role of IL-17 in acute rejection.
  
  
  RESULTS
  Th17 cells and related cytokines (IL-17 and IL-6) were obviously increased in the allograft group (all P < 0.01), whereas Treg cells and related cytokines (IL-10 and transforming growth factor-β1) were markedly lower than those of isograft and control groups (all P < 0.01). In addition, liver grafts in allograft groups rejected acutely (MST, 8.0 ± 1.2 days) accompanied by impaired liver function (AST, ALT, and T-Bili), while isograft groups survived long term (MST, 50.0 ± 3.8 days, all P < 0.01 vs. allograft group). Finally, neutralization of IL-17 in allograft groups significantly prolonged the survival (MST, 32.0 ± 4.8 days, P < 0.01), improved the liver function (AST, ALT, and T-Bili), and increased Treg cells in the liver (all P < 0.01).
  
  
  CONCLUSIONS
  Th17 cells and secreted IL-17 play critical roles in acute rejection after liver grafts. The reduction of IL-17 may be 1 mechanism of immune tolerance after liver transplantation.
authors.affiliation: 1 Department of Hepatobiliary Surgery, Taizhou People's Hospital, the Fifth Affiliate Hospital of Medical School of Nantong University, Taizhou, Jiangsu Province, China. 2 Department of General Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China. 3 Department of Hepatobiliary Surgery, Affiliate Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, China.
authors.forename: Yaxing
authors.initials: Y
authors.lastname: Zhou
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Yang
authors.forename: Hai
authors.initials: H
authors.lastname: Zhang
authors.forename: Jianguo
authors.initials: J
authors.lastname: Jiang
mesh_terms: D000208:Acute Disease; D064591:Allografts; D000818:Animals; D057134:Antibodies, Neutralizing / Q000008:administration & dosage; D006084:Graft Rejection / Q000209:etiology / Q000276:immunology*; D016753:Interleukin-10 / Q000097:blood; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000097:blood / Q000276:immunology; D016031:Liver Transplantation / Q000009:adverse effects*; D018655:Lymphocyte Count; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D053773:Transforming Growth Factor beta1 / Q000097:blood; D023001:Transplantation Tolerance
chemical_list: D057134:Antibodies, Neutralizing; D020381:Interleukin-17; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10