Th17 promotes acute rejection following liver transplantation in rats.
T help cell 17 (Th17), recently identified as a new subset of CD4(+) T cells, has been implicated in autoimmune diseases, tumor immunity, and transplant rejection. To investigate the role of Th17 in acute hepatic rejection, a rat model of allogeneic liver transplantation (Dark Agouti (DA) to Brown Norway (BN)) was established and isogeneic liver transplantation (BN to BN) was used as controls in the study. The expression of Th17-related cytokines in the liver and peripheral blood was determined by immunohistochemistry, flow cytometry, enzyme-linked immunosorbent assay (ELISA), or real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR). Strong expression of interleukin-17A (IL-17A), IL-6, transforming growth factor-β (TGF-β), IL-8, and myeloperoxidase (MPO) was observed in liver allografts. The ratios of Th17 to CD4(+) lymphocytes in the liver and peripheral blood were dramatically increased in the allograft group compared with the control (P<0.01). Secreted IL-17 and IL-6 in liver homogenate and serum were significantly elevated in the allograft group, while secreted TGF-β was increased in liver homogenate and decreased in serum compared with the control (P<0.01). The messenger RNA (mRNA) levels of IL-17, IL-21, and IL-23 were enhanced in the allografts compared with the control (P<0.01). Correlation analysis showed significant correlations between IL-17 and IL-6 and TGF-β and between IL-17 and IL-21 and IL-23. The present study demonstrates that Th17 plays a role in promoting rat liver allograft rejection.
Key Laboratory of Combined Multi-organ Transplantation of Ministry of Public Health, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Xiao-jun
XJ
Xie
Yu-fu
YF
Ye
Lin
L
Zhou
Hai-yang
HY
Xie
Guo-ping
GP
Jiang
Xiao-wen
XW
Feng
Yong
Y
He
Qin-fen
QF
Xie
Shu-sen
SS
Zheng
D000208:Acute Disease; D000818:Animals; D016207:Cytokines / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology*; D008099:Liver / Q000276:immunology* / Q000473:pathology; D016031:Liver Transplantation / Q000009:adverse effects* / Q000276:immunology*; D051381:Rats; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology
D016207:Cytokines