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ABSTRACT:
PROVIDER: PRJNA491725 | ENA |
REPOSITORIES: ENA
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Project description:Host NLRP6 regulates innate immune responses and gastrointestinal (GI) homeostasis. It plays a protective role in pathogenic processes such as intestinal colitis and tumorigenesis in a microbiome dependent manner. Host innate immunity and changes in microbial diversity also play a role in the severity of allo-immune-mediated gastrointestinal pathogenic process, namely graft-versus-host disease (GVHD), the principal toxicity after allogeneic bone marrow transplantation (allo-BMT). Herein, we examined the role of NLRP6 in multiple murine models of allo-BMT. In contrast to its role in intestinal colitis, host NLRP6 aggravated GI GVHD. NLRP6-deficient animals showed improved intestinal barrier function, increased levels of tissue repair associated proteins and preserved Goblet and Paneth cell numbers in the GI tract after allo-BMT. The impact of host NLRP6 deficiency in mitigating GVHD was observed regardless of co-housing, antibiotic treatment, or colonizing littermate germ free wild type (WT) and NLRP6 deficient hosts with fecal microbial transplantation from SPF WT and Nlrp6-/- animals. Chimera studies were performed to assess the role of NLRP6 expression on host hematopoietic and non-hematopoietic cells. The allogeneic [B6Ly5.2→Nlrp6-/-] animals demonstrated significantly improved survival compared to the allogeneic [B6Ly5.2→B6] animals, demonstrating that the absence of NLRP6 in host non-hematopoietic cells is crucial for the protection against GVHD, but did not alter the therapeutic graft-versus-tumor effects after BMT. Our results unveil a novel role for NLRP6 and demonstrate a pathogenic role in GVHD that is independent of variations in its intestinal microbiome in contrast to its well-appreciated microbiome-dependent protective role in intestinal colitis and tumorigenesis.
2018-11-05 | ST001089 | MetabolomicsWorkbench
Project description:RATIONALE: Beclomethasone may be an effective treatment for graft-versus-host disease.
PURPOSE: Phase I/II trial to study the effectiveness of beclomethasone in treating patients who have graft-versus-host disease of the esophagus, stomach, small intestine, or colon.
| 2005776 | ecrin-mdr-crc
Project description:Allogeneic hematopoietic stem cell transplantation remains the most efficacious treatment for many hematological malignancies. However, its therapeutic potential is affected by the most prominent side effect graft versus host disease. Despite advances in the treatment of graft versus host disease in recent years, morbidity and mortality remains high, which requires the development of new treatment approaches. We therefore implemented mouse models to assess potential treatment options for graft versus host disease. In in vivo experiments, we had observed a protective effect of LCN2 on graft versus host disease of the gastrointestinal tract. We also observed higher numbers of anti-inflammatory macrophages in the intestinal tissues of these animals. Therefore, we aimed to determine potentially regulated genes in these cells by using an in vitro approach of LCN2-treated macrophages.
2024-01-24 | GSE226432 | GEO
Project description:Acute graft-versus-host disease (gene expression profiling)
| PRJNA100457 | ENA
Project description:Donor T cells in ovarian graft versus host disease
| PRJNA321441 | ENA
Project description:Metagenomic next-generation sequencing of Graft-versus-Host disease
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Project description:Study of Intestinal microbiota in graft-versus-host disease
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Project description:The macrolide rapamycin is known for its immunosuppressive properties since it inhibits mTOR (mammalian target of rapamycin), which activity affects differentiation and functions of various innate and adaptive immune cells involved in graft-versus-host disease development. Since rapamycin procures immunosuppressive effects on the immune response, rapamycin is an attractive candidate for graft-versus-host disease prevention after allogeneic bone marrow transplantation. Recently, an activating effect of rapamycin on the function of myeloid-derived suppressor cells (MDSCs), a subset of immune suppressive cells of myeloid origin was reported. However, the effect of rapamycin treatment on MDSCs induction and function in the management of graft-versus-host disease is largely unknown. We used an MHC class I and II mismatched parent into F1 bone marrow transplantation mouse model to elucidate the mechanisms of rapamycin on MDSCs in the context of graft-versus-host disease prevention. To define the impact of rapamycin therapy on MDSCs gene expression profile, we performed mircoarray analysis and compared gene expression profiles of ex vivo isolated MDSCs from rapamycin and PBS treated mice
2020-07-21 | GSE141414 | GEO
Project description:The macrolide rapamycin is known for its immunosuppressive properties since it inhibits mTOR (mammalian target of rapamycin), which activity affects differentiation and functions of various innate and adaptive immune cells involved in graft-versus-host disease development. Since rapamycin procures immunosuppressive effects on the immune response, rapamycin is an attractive candidate for graft-versus-host disease prevention after allogeneic bone marrow transplantation We used an MHC class I and II mismatched parent into F1 bone marrow transplantation mouse model to elucidate the mechanisms of rapamycin on T cells in the context of graft-versus-host disease prevention. To define the impact of rapamycin therapy on T cells gene expression profile, we performed mircoarray analysis and compared gene expression profiles of sorted splenic T cells from rapamycin and PBS treated mice
2020-07-22 | GSE141415 | GEO
Project description:Transcriptome analysis of acute graft-versus-host disease in children
| PRJNA706045 | ENA