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Microbiota dictate T cell clonal selection to augment graft-vs-host disease after stem cell transplantation

ABSTRACT: Microbiota dictate T cell clonal selection to augment graft-vs-host disease after stem cell transplantation

PROVIDER: PRJNA1110174 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28989015.fastq.gz	Fastqsanger.gz
	SRR28989016.fastq.gz	Fastqsanger.gz
	SRR28989017.fastq.gz	Fastqsanger.gz
	SRR28989018.fastq.gz	Fastqsanger.gz
	SRR28989019.fastq.gz	Fastqsanger.gz

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Microbiota dictate T cell clonal selection to augment graft-vs-host disease after stem cell transplantation

Project description:Allogeneic T cell expansion is the primary determinant of graft-versus-host disease (GVHD), and current dogma dictates that this is driven by histocompatibility antigen disparities between donor and recipient. This paradigm represents a closed genetic system within which donor T cells interact with peptide-MHC complexes, though clonal interrogation remains challenging due to the sparseness of the T cell repertoire. We developed a Bayesian model using donor and recipient TCR frequencies in murine stem cell transplant systems to define limited common expansion of T cell clones across genetically identical donor-recipient pairs. A subset of donor CD4 T cell clonotypes differentially expanded in identical recipients and were microbiota dependent. Microbiota-specific T cells augmented GVHD lethality and could target microbial antigen presented by gastrointestinal epithelium during an alloreactive response. The microbiota thus serves as a source of cognate antigen that contributes to clonotypic T cell expansion and the induction of GVHD independent of donor-recipient genetics.

2024-06-03 | GSE267178 | GEO

BLUEPRINT DNA methylation profiles of graft donors in allogenic hematopoietic stem cell transplantation

Project description:Allogenic hematopoietic stem cell transplantation (HSCT) is a curative treatment for many hematological conditions. Acute graft-versus-host disease (aGVHD) is a prevalent immune-mediated complication following HSCT. Current diagnostic biomarkers that correlate with aGVHD severity, progression, and therapy response in graft recipients are insufficient. We investigated whether epigenetic marks measured in peripheral blood of healthy graft donors stratify aGVHD severity in HLA-matched sibling recipients prior to HSCT. We measured genome-wide DNA methylation levels in peripheral blood of 91 HSCT donors using Illumina Infinium HumanMethylation450 BeadChips. We showed that epigenetic signatures underlying aGVHD severity in recipients correspond to immune pathways relevant to aGVHD etiology. We identified distinct DNA methylation marks in graft donors that are associated with aGVHD severity status in recipients. Together, our findings suggest that ‘epigenetic matching’ of HSCT donor-recipient pairs in a clinical setting may be used in conjunction with genetic matching to inform both donor selection and transplantation strategy, with the ultimate aim of improving patient outcome.

| EGAS00001001287 | EGA

Cyclophosphamide for Prevention of Graft-Versus-Host Disease After Allogeneic Peripheral Blood Stem Cell Transplantation in Patients With Hematological Malignancies

Project description:This phase II trial studies how well cyclophosphamide works in preventing chronic graft-versus-host disease after allogeneic peripheral blood stem cell transplant in patients with hematological malignancies. Giving chemotherapy and total-body irradiation before transplantation helps stop the growth of cancer cells and prevents the patient’s immune system from rejecting the donor’s stem cells. Healthy stem cells from a donor that are infused into the patient help the patient’s bone marrow make blood cells; red blood cells, white blood cells, and platelets. Sometimes, however, the transplanted donor cells can cause an immune response against the body’s normal cells, which is called graft-versus-host disease (GVHD). Giving cyclophosphamide after transplant may prevent this from happening or may make chronic GVHD less severe.

| 2112331 | ecrin-mdr-crc

Single-cell clonal tracking of persistent T-cells in allogeneic hematopoietic stem cell transplantation

Project description:The critical balance between intended and adverse effects in allogeneic hematopoietic stem cell transplantation (alloHSCT) depends on the fate of individual donor T‐cells. To this end, we tracked αβT‐cell clones during stem cell mobilization treatment with granulocyte-colony stimulating factor (G-CSF) in healthy donors and during immune reconstitution after transfer to transplant recipients. More than 250 αβT‐cell clones were tracked from donor to recipient. These clones consisted almost exclusively of CD8+ effector memory T cells (CD8TEM), which exhibited a different transcriptional signature with enhanced effector and cytotoxic functions compared to other CD8TEM. Importantly, these distinct and persisting clones could already be delineated in the donor. We confirmed these phenotypes on the protein level and their potential for selection from the graft. Thus, we identified a transcriptional signature associated with persistence and expansion of donor T-cell clones after alloHSCT that may be exploited for personalized graft manipulation strategies in future studies.

2023-01-27 | GSE222633 | GEO

Pre-Transplant recipients’ clinical and immunological features are independently associated with the development of delayed graft function in kidney transplantation

Project description:Delayed graft function (DGF) is associated with a reduced graft survival. Donors' features have been always considered as key pathogenic factors in this setting. The aim of our study was to evaluate the role of recipients' characteristics in the development of DGF. We prospectively enrolled 932 kidney graft recipients from 466 donors. A total of 226 recipients experienced DGF. Among the 466 donors, in 290 both recipients presented with early graft function (EGF, group A), in 50 both recipients experienced DGF (group B) and in 126 one recipient presented with DGF and the other with EGF (group C). In group C we randomly selected 7 couples of DGF/EGF recipients. In these patients, circulating mononuclear cells were harvested before transplantation and their transcriptomic profile was investigated by a microarray approach. Results were validated by qPCR in an independent group of EGF/DGF couples.

2022-12-22 | E-MTAB-10747 | biostudies-arrayexpress

CpG islands and GC content dictate nucleosome depletion in a transcription independent manner at mammalian promoters

Project description:This SuperSeries is composed of the following subset Series: GSE38560: CpG islands and GC content dictate nucleosome depletion in a transcription independent manner at mammalian promoters (RNA-seq) GSE38561: CpG islands and GC content dictate nucleosome depletion in a transcription independent manner at mammalian promoters (ChIP-seq) GSE38562: CpG islands and GC content dictate nucleosome depletion in a transcription independent manner at mammalian promoters (genomic SEQ) GSE38563: CpG islands and GC content dictate nucleosome depletion in a transcription independent manner at mammalian promoters (MNase-seq) GSE38564: CpG islands and GC content dictate nucleosome depletion in a transcription independent manner at mammalian promoters (5) Refer to individual Series

2012-06-11 | E-GEOD-38577 | biostudies-arrayexpress

Transcription profiling of mononuclear cells from patients undergoing allogenic hematopoitic cell transplantation to identify signatures of acute graft-versus-host disease

Project description:To assess if gene expression signatures could predict acute graft-versus-host disease, we examined the global gene expression profiles of peripheral blood mononuclear cells at day +14 post-transplantation from 94 patients undergoing allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning.

2010-06-09 | E-MEXP-1824 | biostudies-arrayexpress

Transcriptional analysis for cell-cell communication during graft union development in Arabidopsis

Project description:Grafting is an ancient cloning method that has been used widely for thousands of years in agricultural practices. However, the molecular mechanisms for graft union development are still largely unknown. The developmental stage of graft union was characterized based on micrografting method. Microarray data revealed a signal exchange process between cells of scion and stock at 1dag, which reestablished the communication network in graft union. This process was concomitant with the cleaning of cell debris, and both of the processes were initiated by a wound-induced program. The results demonstrate the feasibility and potential power of investigating various plant developmental processes by this method and represent a primary and significant step in interpretation of the molecular mechanisms underlying graft union development. WT/WT seedling grafts of 22-26 hours after grafting were collected for microarray, intact WT seedlings and ungrafted scions and stocks were as control. All three types of sample, grafts (marked as A: whole graft), ungrafted scions and stocks (marked as B: mixture of ungrafted scions and stocks) and intact seedlings (marked as C: whole seedling), were collected at the same time of 22-26 hours after grafting. For sample B, scions and stocks were cut at the same time during grafting. For sample C, intact seedlings were also reserved during grafting. Data were firstly compared between sample A and C, differential expressed probe sets were than tested based on A and B to obtain graft-specific probes.

2012-05-02 | E-GEOD-36447 | biostudies-arrayexpress

Faecal Microbiota Transplantation After Allogeneic Stem Cell Transplantation

Project description:The aim of this study is to assess the Fecal Microbiota Transplantation (FMT) efficacy in the prevention of allogeneic hematopoietic stem cell transplantation (allo-HSCT) complications and particularly Graft versus Host Disease (GvHD). The hypothesis of this study is that allogeneic FMT may improve outcomes of these patients.

| 2381286 | ecrin-mdr-crc

Macrophage infiltration induced by donor hypovolemia protects against severe primary graft dysfunction in mouse lung transplantation

Project description:BACKGROUND: Hypovolemia is common in lung donors before or after brain death. However, its impact on primary graft function (PGD) remains obscure. METHODS: A clinically relevant two-hit model of PGD was established by integrating hypovolemic shock (HS) and cold ischemia-reperfusion in a mouse model of orthotopic lung transplantation (LTx) from C57BL/6 to Balb/c. At -48 hours, HS was induced to donor by withdrawal of blood from femoral artery and keeping the mean arterial pressure at 15±5 mmHg for 4 h. At -24 hours, donor lungs were retrieved from mice with or without HS and stored at 0ºC until transplantation. CD11b-DTR mice were used as donor and treated with Diphtheria Toxin (DT) to deplete graft-infiltrating macrophages. RESULTS: HS mainly caused macrophage-predominant infiltration around pulmonary artery injury systemic inflammatory response, but little impairment of lung function even if in combination with cold ischemia-reperfusion. Transcriptional profiling showed HS pretreatment increased pulmonary damage and alveolar remodeling but ameliorated inflammatory infiltration when compared to one-hit model of 12 hours cold ischemia-reperfusion injury. The allografts with donor DT-treatment one day ahead of HS showed injury and dysfunction at donation and worsened further at 24 hours reperfusion, whereas the allografts with recipient DT-treatment immediately after transplantation showed similar function and histology to the control treated with saline. CONCLUSION: Donor hypovolemia causes pulmonary artery injury and infiltration but has little impact on allograft function, even in combination with 24 h cold ischemia. Graft-infiltrating macrophages are critical in protecting graft from HS-induced injury and cold ischemia-reperfusion injury.

2022-03-30 | GSE156322 | GEO

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