scholarly journals High Mobility Group Box 1 Contributes to the Acute Rejection of Liver Allografts by Activating Dendritic Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Yi Chen ◽  
Wenmin Zhang ◽  
Hui Bao ◽  
Wubing He ◽  
Lihong Chen

Acute rejection induced by the recognition of donor alloantigens by recipient T cells leads to graft failure in liver transplant recipients. The role of high mobility group box 1 (HMGB1), an inflammatory mediator, in the acute allograft rejection of liver transplants is unknown. Here, rat orthotopic liver transplantation was successfully established to analyze the expression pattern of HMGB1 in liver allografts and its potential role in promoting the maturation of dendritic cells (DCs) to promote T cell proliferation and differentiation. Five and 10 days after transplantation, allografts showed a marked upregulation of HMGB1 expression accompanied by elevated levels of serum transaminase and CD3+ and CD86+ inflammatory cell infiltration. Furthermore, in vitro experiments showed HMGB1 increased the expressions of co-stimulatory molecules (CD80, CD83, and MHC class II) on bone marrow-derived DCs. HMGB1-pulsed DCs induced naive CD4+ T cells to differentiate to Th1 and Th17 subsets secreting IFN-γ and IL-17, respectively. Further in vivo experiments confirmed the administration of glycyrrhizic acid, a natural HMGB1 inhibitor, during donor liver preservation had therapeutic effects by reducing inflammation and hepatocyte damage reflected by a decline in serum transaminase and prolonged allograft survival time. These results suggest the involvement of HMBG1 in acute liver allograft rejection and that it might be a candidate therapeutic target to avoid acute rejection after liver transplantation.

2005 ◽  
Vol 5 (10) ◽  
pp. 2393-2402 ◽  
Author(s):  
J. Kwekkeboom ◽  
T. Tha-In ◽  
W.M.W. Tra ◽  
W. Hop ◽  
P.P.C. Boor ◽  
...  

2019 ◽  
Vol 213 ◽  
pp. 55-61 ◽  
Author(s):  
Ke Zhang ◽  
Yan-Ling Sun ◽  
Shuang-Nan Zhou ◽  
Ruo-Nan Xu ◽  
Zhen-Wen Liu ◽  
...  

Hepatology ◽  
2020 ◽  
Author(s):  
Rebecca A. Sosa ◽  
Allyson Q. Terry ◽  
Fady M. Kaldas ◽  
Yi‐Ping Jin ◽  
Maura Rossetti ◽  
...  

Oncotarget ◽  
2016 ◽  
Vol 7 (25) ◽  
pp. 37893-37905 ◽  
Author(s):  
Hao Liu ◽  
Pasquale Patrick Innamarato ◽  
Krithika Kodumudi ◽  
Amy Weber ◽  
Satoshi Nemoto ◽  
...  

PLoS ONE ◽  
2014 ◽  
Vol 9 (11) ◽  
pp. e112135 ◽  
Author(s):  
Ying Wang ◽  
Min Zhang ◽  
Zhen-Wen Liu ◽  
Wei-Guo Ren ◽  
Yan-Chao Shi ◽  
...  

2010 ◽  
Vol 91 (1) ◽  
pp. 43-53 ◽  
Author(s):  
Lihua Duan ◽  
Cong-Yi Wang ◽  
Jie Chen ◽  
Quan Gong ◽  
Ping Zhu ◽  
...  

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Toshiaki Nakano ◽  
Shigeru Goto ◽  
Chia-Yun Lai ◽  
Li-Wen Hsu ◽  
Hui-Peng Tseng ◽  
...  

Concanavalin A (Con A) is a lectin originating from the jack-bean and well known for its ability to stimulate T cells and induce autoimmune hepatitis. We previously demonstrated the induction of immunosuppressive antinuclear autoantibody in the course of Con A-induced transient autoimmune hepatitis. This study aimed to clarify the effects of Con A-induced hepatitis on liver allograft rejection and acceptance. In this study, we observed the unique phenomenon that the induction of transient de novo autoimmune hepatitis by Con A injection paradoxically overcomes the rejection without any immunosuppressive drug and exhibits significantly prolonged survival after orthotopic liver transplantation (OLT). Significantly increased titers of anti-nuclear Abs against histone H1 and high-mobility group box 1 (HMGB1) and reduced donor specific alloantibody response were observed in Con A-injected recipients. Induction of Foxp3 and IL-10 in OLT livers of Con A-injected recipients suggested the involvement of regulatory T cells in this unique phenomenon. Our present data suggest the significance of autoimmune responses against nuclear histone H1 and HMGB1 for competing allogeneic immune responses, resulting in the acceptance of liver allografts in experimental liver transplantation.


2006 ◽  
Vol 81 (1) ◽  
pp. 59-66 ◽  
Author(s):  
De Yang ◽  
Qian Chen ◽  
Huan Yang ◽  
Kevin J. Tracey ◽  
Michael Bustin ◽  
...  

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