Th17 promotes acute rejection following liver transplantation in rats

Abstract

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.

IL-17 Axis Driven Inflammation in Non-Alcoholic Fatty Liver Disease Progression

“…Increased IL-17A production was reported in diverse human liver diseases, including alcoholic liver disease [60], acute liver injury [66], chronic hepatitis B and C [67, 68], primary biliary cirrhosis [69, 70], hepatocellular carcinoma [71], and acute liver transplant rejection [72, 73]. Further, the role of the IL-17 axis in the pathogenesis of liver disease has been extensively evaluated in multiple mouse models of liver injury.…”

Liver Injury in Psoriasis Patients Receiving Ustekinumab: A Retrospective Study of 44 Patients Treated in the Clinical Practice Setting

“…29 Finally, T H 17 cells are involved in rejection of liver allografts in rats. 30 Therefore, modulation of T H 17 could lead to improvement in many liver diseases. We did not observe any worsening of liver disease that was present at the start of treatment with UTK.…”

Role of IL-21 signaling pathway in transplant-related biology

“…In rat liver transplant model (Dark Agouti → Brown Norway), allogeneic immune responses also caused a significant increase of intragraft IL-21 mRNA expression [8]. In addition, an increased expression of IL-21 could be detected within draining lymph nodes in the transplanted corneal recipients (C57BL/6 → Balb/c) [12].…”

“…In recent years, interleukin-21 (IL-21) is being highlighted as an important pro-inflammatory cytokine, which is strongly involved in transplant immunobiology [4][5][6][7][8]. Nevertheless, its role and underlying mechanisms remain undefined well.…”