Project description:Wildtype (WT) BALB/c mice were treated with allogeneic hematopoietic cell transplantation (allo-HCT) in order to induce acute GVHD. C57BL/6 mice were used bone marrow (BM) and T cell donor mice. We studied the effect of oral hBD-2 treatment versus vehicle (PBS) control treatment on the gene expression in the colon, as main GVHD target organ.
Project description:In this experiment, we studied how human beta defensin-2 (hBD-2) affects gene expression of T cells. Murine splenic C57BL/6 CD4/CD8 T cells were stimulated with anti-CD3/anti-CD28 beads and hBD-2 or vehicle (PBS) control for 48h before RNA isolation
Project description:A promise of cell replacement therapy using pluripotent stem cells (PSCs) such as embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) as donor source has been increased. However, particularly when ESCs were used, immune suppression should be required because the donor-recipient combination would be allogeneic. In this study, we examined a concept that some immunosuppressive cells could be induced from PSCs and those cells could prevent allogeneic immune rejection of the PSCs-based transplantation. In fact, we successfully induced immunosuppressive cells that resemble M2 macrophages in terms of cell surface molecule and gene expressions. They efficiently suppressed allogeneic T cell proliferative responses, at least partly, in nitric oxide dependent manner. We applied these cells to in vivoallogeneic transplantation and found that they substantially prolonged ESCs-derived graft survival. These results open a new insight for development of a practical immune-regulatory strategy in cell replacement therapy using PSCs. Difference of the gene expression between ESdSC and ESdDC was analyzed. Two independent experiment were performed.
Project description:Administration of azithromycin after allogeneic hematopoietic stem cell transplantation for hematological malignancies has been associated with relapse in a randomized phase 3 controlled clinical trial. Studying 240 samples from patients randomized in this trial is a unique opportunity to better understand the mechanisms underlying relapse, the first cause of mortality after transplantation. We used multi-omics on patients' samples to decipher immune alterations associated with azithromycin intake and post-transplant relapsed malignancies. Azithromycin was associated with a network of altered energy metabolism pathways and immune subsets, including T cells biased toward immunomodulatory and exhausted profiles. In vitro, azithromycin exposure inhibited T cells cytotoxicity against tumor cells and impaired T cells metabolism through glycolysis inhibition, mitochondrial genes downregulation, and immunomodulatory genes upregulation, notably SOCS1. These results highlight that azithromycin directly affects immune cells that favor relapse, which raises caution about long-term use of azithromycin treatment in patients at high risk of malignancies.
Project description:A promise of cell replacement therapy using pluripotent stem cells (PSCs) such as embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) as donor source has been increased. However, particularly when ESCs were used, immune suppression should be required because the donor-recipient combination would be allogeneic. In this study, we examined a concept that some immunosuppressive cells could be induced from PSCs and those cells could prevent allogeneic immune rejection of the PSCs-based transplantation. In fact, we successfully induced immunosuppressive cells that resemble M2 macrophages in terms of cell surface molecule and gene expressions. They efficiently suppressed allogeneic T cell proliferative responses, at least partly, in nitric oxide dependent manner. We applied these cells to in vivoallogeneic transplantation and found that they substantially prolonged ESCs-derived graft survival. These results open a new insight for development of a practical immune-regulatory strategy in cell replacement therapy using PSCs.