title: Thrombomodulin alleviates murine GVHD in association with an increase in the proportion of regulatory T cells in the spleen.
abstract: Recombinant human soluble thrombomodulin (rTM), a potent anticoagulant, has been used for the treatment of disseminated intravascular coagulation in Japan since 2008. Interestingly, rTM possesses anti-inflammatory and cytoprotective functions. This study examined whether rTM alleviates GVHD in a murine hematopoietic SCT (HSCT) model. Use of rTM significantly improved the survival of mice on day 28 of transplantation (survival rate 70% in rTM - treated mice vs 35% in control, P<0.05) in association with a significant decrease in plasma levels of IL-6, IFN-γ and high-mobility group B1 DNA-binding protein on day 7 of HSCT. Intriguingly, the proportion of regulatory T cells in the spleen was significantly increased in rTM-treated mice on day 7 of transplantation compared with control diluent-treated mice. In addition, elevated plasma levels of TM and fibrin/fibrinogen degradation product were noted in HSCT-recipient mice, suggesting coagulopathy caused by endothelial cell damage in this GVHD model. The use of rTM potently decreased these levels. Importantly, rTM did not hamper the anti-GVL and engraftment of hematopoietic cells. Taken together, the use of rTM may prevent GVHD and serve as a potential therapeutic strategy to improve clinical outcomes in individuals who receive HSCT.
authors.affiliation: Department of Hematology and Respiratory Medicine, Kochi University, Nankoku, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ikezoe
authors.affiliation: Department of Hematology and Respiratory Medicine, Kochi University, Nankoku, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Hematology and Respiratory Medicine, Kochi University, Nankoku, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Nishioka
authors.affiliation: Department of Hematology and Respiratory Medicine, Kochi University, Nankoku, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Yokoyama
mesh_terms: D064591:Allografts; D000818:Animals; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D051379:Mice; D011994:Recombinant Proteins / Q000627:therapeutic use; D013154:Spleen / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D018180:Thrombomodulin / Q000627:therapeutic use*
chemical_list: D011994:Recombinant Proteins; C546931:THBD protein, human; D018180:Thrombomodulin