Experimental studyImmunosuppressionKüpffer Cells Promote Acute Rejection via Induction of Th17 Differentiation in Rat Liver Allografts
Section snippets
Animals
Inbred male Dark Agouti (DA) and Brown Norway (BN) rats aged 12 weeks and weighing 200 to 250 g were purchased from Beijing Vital River Company (Beijing, China). The animals were housed under standard animal care conditions, and received food and water ad libitum. The study was approved by the China Association of Laboratory Animal Care and the Institutional Animal Care Committee.
Rats were assigned to 3 treatment groups: an isograft group (BN to BN liver transplantation), an allograft group (DA
Increased Infiltration of Küpffer cells and Th17 cells Into Liver Allografts
The rejection of allogeneic liver grafts (DA to BN) was compared with that of isografts (BN to BN). No signs of rejection were observed in isograft recipients, whereas allograft hosts exhibited severe acute rejection accompanied by elevated serum concentrations of ALT and AST. Extensive intragraft mononuclear cell infiltration and severe liver damage were also observed in allograft recipients (data not shown). To analyze intragraft infiltration by Küpffer cells and IL-17–producing cells in
Discussion
The role of Küpffer cells in liver allograft rejection has been controversial. Some studies have demonstrated that Küpffer cells participate in the rejection reaction by mediating potent proinflammatory activities and acting as antigen-presenting cells.22, 23, 24 In contrast, other studies have demonstrated that Küpffer cells have a key role in development of immune tolerance by inducing T-cell apoptosis or producing IL-10 and TGF-β.25, 26 In the present study, an increased number of
Acknowledgements
This study was supported by grant 2009CB522403 from the National Basic Research Program (973) of China, grant 30730085 from the Key Program of the National Natural Science Foundation of China, and grant 30972795 from the National Natural Science Foundation of China.
References (31)
Development in motion: helper T cells at work
Cell
(2007)- et al.
The role of the IL23/IL17 axis in bronchiolitis obliterans syndrome after lung transplantation
Am J Transplant
(2008) - et al.
A pathogenic role of IL-17 at the early stage of corneal allograft rejection
Transpl Immunol
(2009) - et al.
Hepatic allograft–derived Kupffer cells regulate T cell response in rats
Liver Transpl
(2003) - et al.
Hepatic allograft-derived Kupffer cells regulate T cell response in rats
Liver Transpl
(2003) - et al.
Activated Kupffer cells play an important role in intra-hepatic Th1-associated necro-inflammation in concanavalin A–induced hepatic injury in mice
Hepatol Res
(2003) Scientific Registry of Transplant Recipients
- et al.
The role of macrophages in allograft rejection
Transplantation
(2005) Banff schema for grading liver allograft rejection: an international consensus document
Hepatology
(1997)- et al.
The role of CD4+ T-cell subsets in determining transplantation rejection or tolerance
Immunol Rev
(2001)
Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells
Nature
Transforming growth factor–beta induces development of the T(H)17 lineage
Nature
A novel role of CD4 Th17 cells in mediating cardiac allograft rejection and vasculopathy
J Exp Med
Evidence for the early involvement of interleukin 17 in human and experimental renal allograft rejection
J Pathol
IL-17 expression as a possible predictive parameter for subclinical renal allograft rejection
Transpl Int
Cited by (9)
Galectin-1 attenuates hepatic ischemia reperfusion injury in mice
2019, International ImmunopharmacologyCitation Excerpt :After 7 days of culture, adherent macrophages were harvested for further experiments. Non-parenchymal cells from mouse liver were isolated by a 2-step collagenase perfusion, as described in our previous study [15]. Positive selection of F4/80+ cells (hepatic macrophages) from nonparenchymal cells was performed using the QuadroMACS column separation kit (Miltenyi Biotech, Cambridge, MA) [16].
Galectin-9 in Combination with EX-527 Prolongs the Survival of Cardiac Allografts in Mice after Cardiac Transplantation
2015, Transplantation ProceedingsCitation Excerpt :These data suggest that an increased level of circulating TH17 cells may be a novel marker for AR. Earlier studies demonstrated that TH1 cells are responsible for AR, and some recent studies have suggested that TH17 cells may also be involved in the process [32–35]. The contribution of TH17 cells to clinical AR has not yet been well documented, but animal studies have shown that TH17 cells induce tissue damage by stimulating inflammatory cells to release proinflammatory cytokines and accelerate the development of allograft vasculopathy [33].
Rejection After Transplantation
2015, Transplantation of the Liver: Third EditionKupffer cells contribute to concanavalin A-induced hepatic injury through a Th1 but not Th17 type response-dependent pathway in mice
2011, Hepatobiliary and Pancreatic Diseases InternationalAmygdalin reduces lipopolysaccharide-induced chronic liver injury in rats by down-regulating PI3K/AKT, JAK2/STAT3 and NF-κB signalling pathways
2019, Artificial Cells, Nanomedicine and BiotechnologyImmune function of nonparenchymal liver cells
2016, Genetics and Molecular Research