High expression of heme oxygenase-1 in target organs may attenuate acute graft-versus-host disease through regulation of immune balance of TH17/Treg

The high incidence of acute graft-versus-host disease (aGVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Grades III and IV aGVHD are the leading causes of death in allo-HSCT recipients. Heme oxygenase-1(HO-1) has anti-inflammatory and immune-regulatory functions. In this study, we evaluated the none GVHD and grade I-IV patients samples which were collected at the first re-examination after successful allo-HSCT, we found that expressions of HO-1 mRNA in the bone marrow and peripheral blood mononuclear cells of allo-HSCT recipients who had subsequent non-GVHD and grade I aGVHD were significantly higher than those in patients with Grade III-IV aGVHD. We then demonstrated that enhanced expression of HO-1 in target organs by infusing HO-1-gene-modified Mesenchymal stem cells (MSCs) alleviated the clinical and histopathological severity of aGVHD in experimental mice. Flow cytometry revealed a higher expression of Treg cells and a lower expression of TH17 cells in splenic and lymph node tissues of mice with enhanced HO-1 expression, as compared to that in the aGVHD mice. This was further substantiated by lower expression levels of ROR-Yt and IL-17A mRNA, and higher levels of Foxp3 mRNA in the splenic tissue of mice with enhanced HO-1 expression. Our results indicate that high expression of HO-1 may reduce the severity of aGVHD by regulation of the TH17/Freg balance. (C) 2016 Elsevier B.V. All rights reserved.