Protective Effects of Heme Oxygenase-1 Expression in Patients and Mice with Acute Graft-Versus-Host Disease?

Abstract

The development of acute graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is facilitated by damage-associated molecular patterns (DAMPs) released upon tissue damage due to the conditioning regimen. Heme oxygenase-1 (HO-1) is a stress-inducible enzyme responsible for the breakdown of the DAMP cell-free heme. HO-1 plays a protective role in diseases characterized by systemic inflammation such as sepsis, but its role in the development of acute GvHD remains unclear. Here, we characterized the expression of HO-1 in a small cohort of allo-HSCT recipients with and without acute GvHD. We found HO-1 protein levels in plasma to be elevated in patients just before their acute GvHD diagnosis compared with baseline. Furthermore, HO-1 mRNA expression was increased in patients with acute GvHD at 1 and 3 months after allogeneic HSCT compared with patients without acute GvHD. Finally, induction of HO-1 in a humanized mouse model for acute GvHD led to lower disease scores and a reduction in weight loss. Overall, our data indicate that HO-1 expression is increased in patients with acute GvHD and that HO-1 induction might be able to provide protection against the disease, warranting further research into HO-1 as a target for clinical application.