TY - JOUR
T1 - Heme Oxygenase-1 dictates innate – adaptive immune phenotype in human liver transplantation
AU - Kadono, Kentaro
AU - Dery, Kenneth J.
AU - Hirao, Hirofumi
AU - Ito, Takahiro
AU - Kageyama, Shoichi
AU - Nakamura, Kojiro
AU - Oncel, D.
AU - Aziz, Antony
AU - Kaldas, Fady M.
AU - Busuttil, Ronald W.
AU - Kupiec-Weglinski, Jerzy W.
N1 - Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/8/15
Y1 - 2019/8/15
N2 - Liver transplantation (LT) has become the standard of care for patients with end-stage liver disease and those with hepatic malignancies, while adaptive immune-dominated graft rejection remains a major challenge. Despite potent anti-inflammatory and cytoprotective functions of heme oxygenase-1 (HO-1) overexpression upon innate immune-driven hepatic ischemia reperfusion injury, its role in adaptive immune cell-driven responses remains to be elucidated. We analyzed human biopsies from LT recipients (n = 55) to determine putative association between HO-1 levels and adaptive/co-stimulatory gene expression programs in LT. HO-1 expression negatively correlated with innate (CD68, Cathepsin G, TLR4, CXCL10), adaptive (CD4, CD8, IL17) and co-stimulatory (CD28, CD80, CD86) molecules at the graft site. LT recipients with high HO-1 expression showed a trend towards improved overall survival. By demonstrating the association between graft HO-1 levels and adaptive/co-stimulatory gene programs, our study provides important insights to the role of HO-1 signaling in LT patients.
AB - Liver transplantation (LT) has become the standard of care for patients with end-stage liver disease and those with hepatic malignancies, while adaptive immune-dominated graft rejection remains a major challenge. Despite potent anti-inflammatory and cytoprotective functions of heme oxygenase-1 (HO-1) overexpression upon innate immune-driven hepatic ischemia reperfusion injury, its role in adaptive immune cell-driven responses remains to be elucidated. We analyzed human biopsies from LT recipients (n = 55) to determine putative association between HO-1 levels and adaptive/co-stimulatory gene expression programs in LT. HO-1 expression negatively correlated with innate (CD68, Cathepsin G, TLR4, CXCL10), adaptive (CD4, CD8, IL17) and co-stimulatory (CD28, CD80, CD86) molecules at the graft site. LT recipients with high HO-1 expression showed a trend towards improved overall survival. By demonstrating the association between graft HO-1 levels and adaptive/co-stimulatory gene programs, our study provides important insights to the role of HO-1 signaling in LT patients.
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U2 - 10.1016/j.abb.2019.07.007
DO - 10.1016/j.abb.2019.07.007
M3 - Article
C2 - 31299184
AN - SCOPUS:85068735613
SN - 0003-9861
VL - 671
SP - 162
EP - 166
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
ER -