HO-1-Transduced Mesenchymal Stem Cells Attenuate aGVHD By Inhibiting HIF-1α /ROR-γt and then Down-Regulate Proportion of TH17/Treg

Abstract Background. In acute graft versus host disease, the balance pattern of Treg/Thl7 cells are destroyed, leading to a series of inflammation and damage to the body, greatly affect the survival of allogeneic hematopoietic stem cell transplantation patients. Mesenchymal stem cells can regulate the body's balance of TH17/Treg cells, clinically used to prevent and treat aGVHD.But between immune adjustment ability of mesenchymal stem cells in clinical trials have not been shown to efficiently prevent and treatment of GVHD. HO - 1 as a significant anti-inflammatory and immunosuppressive molecules in rats and human MSC played a crucial role in immune suppression function.In this article, we discuss slow virus in mice mediated transfection MSC HO-1 key nuclear transcription factor can inhibit the TH17 STAT3 activation to further decline, the proportion of TH17/Treg and whether more effectively adjust the related the secretion of cytokines to alleviate aGVHD caused by inflammation of the target organ damage, in addition to observe the clinical patients undergoing allogeneic transplantation patients occurred aGVHD HO-1 high expression and the relationship between the expression of STAT3 and the secretion of peripheral blood serum of TH17/Treg related factors. Methods.Lentivirus transfection raised for rat mesenchymal stem cells between the expression of HO-1, trailing edge vein injection of mice treated, fluorescence microscopy MSC colonize the target organs of mice, pathological biopsy to detect target organ damage, immunohistochemical detection of target organs and the spleen and the expression of pSTAT3, HO-1 flow cytometry to detect the spleen, drainage of lymph node ratio of TH17/Treg cells, Realtime PCR and ELISA to detect the related inflammatory factor levels. Results. The mouse in accepting HO-1 high expression of mesenchymal stem cells after infusion, significantly reduce aGVHD, immunohistochemical results show that the main target organs damage in the expression of HO-1 is inversely proportional to the expression of STAT3 and spleen pSTAT3 protein and total level of STAT3 protein was lower than other groups, the spleen and lymph nodes of TH17/Treg proportion are lower than other groups, IL-17 A, ROR-ϒt mRNA level and serum concentration is lower than other groups, FOXP3, TGF-β mRNA and serum concentration is higher than in the rest of the group. Conclusions. These results suggest that activation of HO - 1 May improve the anti-inflammatory and immune suppression ability of MSC, and perhaps by inhibiting the phosphorylation of STAT3, cut ratio of TH17/Treg cells, promote reduce aGVHD. Disclosures No relevant conflicts of interest to declare.