Heme Oxygenase-1 dictates innate - adaptive immune phenotype in human liver transplantation

Arch Biochem Biophys. 2019 Aug 15:671:162-166. doi: 10.1016/j.abb.2019.07.007. Epub 2019 Jul 9.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptive Immunity* / genetics
  • Adult
  • Female
  • Gene Expression Regulation / immunology
  • Heme Oxygenase-1 / metabolism*
  • Humans
  • Immunity, Innate* / genetics
  • Liver Transplantation*
  • Male
  • Signal Transduction / immunology
  • Survival Analysis

Substances

  • Heme Oxygenase-1