title: High expression of heme oxygenase-1 in target organs may attenuate acute graft-versus-host disease through regulation of immune balance of TH17/Treg.
abstract: 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-Υt 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/Treg balance.
authors.affiliation: Graduate School, Guizhou Medical University, PR China.
authors.forename: Meisheng
authors.initials: M
authors.lastname: Yu
authors.affiliation: Guizhou Province Laboratory of Hematopoietic Stem Cell Transplantation Centre, PR China; Department of Hematology, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550004, PR China. Electronic address: wangjishi9646@163.com.
authors.forename: Jishi
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Affiliated Baiyun Hospital of Guizhou Medical University, Guiyang, Guizhou 550058, PR China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Fang
authors.affiliation: Graduate School, Guizhou Medical University, PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.affiliation: Graduate School, Guizhou Medical University, PR China.
authors.forename: Shuya
authors.initials: S
authors.lastname: Chen
authors.affiliation: Graduate School, Guizhou Medical University, PR China.
authors.forename: Nana
authors.initials: N
authors.lastname: Zhe
authors.affiliation: Graduate School, Guizhou Medical University, PR China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Lin
authors.affiliation: Guizhou Province Laboratory of Hematopoietic Stem Cell Transplantation Centre, PR China.
authors.forename: Yaming
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Guizhou Province Laboratory of Hematopoietic Stem Cell Transplantation Centre, PR China.
authors.forename: Jiangyuan
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Pharmacy, Affiliated Baiyun Hospital of Guizhou Medical University, Guiyang, Guizhou 550058, PR China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhou
mesh_terms: D000208:Acute Disease; D000818:Animals; D001853:Bone Marrow / Q000378:metabolism*; D002478:Cells, Cultured; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D006086:Graft vs Host Disease / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D056747:Immunomodulation; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D020381:Interleukin-17; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D051547:Heme Oxygenase-1
keywords: Acute graft-versus-host disease; Heme oxygenase-1; Mesenchymal stem cell; TH17; Treg