Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Prevention of acute graft-versus-host disease via single-dose administration of bioengineered extracellular vesicles [scRNA-seq]

ABSTRACT: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapy for various hematological and immunologic diseases, but acute graft-versus-host disease (aGVHD) remains a major cause of morbidity and mortality. We previously discovered in patients and murine models that higher levels of pro-inflammatory signals before stem cell infusion are associated with the severity of aGVHD. Here, we show that extracellular vesicles (EVs) mediate the intracellular delivery of SOCS3 (suppressor of cytokine signaling 3), resulting in reduced inflammatory signaling and macrophage/dendritic cell (DC) activation. Furthermore, single-dose treatment with engineered SOCS3-loaded EVs (eEVs) significantly prevented aGVHD and increased survival in multiple murine models without compromising graft-versus-leukemia activity. Mechanistically, single-cell transcriptomics revealed that eEVs induced transcriptional features associated with an immunoregulatory milieu in recipients before allo-HSCT, and then suppressed excessive immune responses, resulting in aGVHD alleviation. In summary, delivery of SOCS3 via EVs represents a promising avenue for aGVHD prophylaxis, with great potential to improve allo-HSCT outcomes.

ORGANISM(S): Mus musculus

PROVIDER: GSE346929 | GEO | 2026/09/11

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Prevention of acute graft-versus-host disease via single-dose administration of bioengineered extracellular vesicles

Project description:Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapy for various hematological and immunologic diseases, but acute graft-versus-host disease (aGVHD) remains a major cause of morbidity and mortality. We previously discovered in patients and murine models that higher levels of pro-inflammatory signals before stem cell infusion are associated with the severity of aGVHD. Here, we show that extracellular vesicles (EVs) mediate the intracellular delivery of SOCS3 (suppressor of cytokine signaling 3), resulting in reduced inflammatory signaling and macrophage/dendritic cell (DC) activation. Furthermore, single-dose treatment with engineered SOCS3-loaded EVs (eEVs) significantly prevented aGVHD and increased survival in multiple murine models without compromising graft-versus-leukemia activity. Mechanistically, single-cell transcriptomics revealed that eEVs induced transcriptional features associated with an immunoregulatory milieu in recipients before allo-HSCT, and then suppressed excessive immune responses, resulting in aGVHD alleviation. In summary, delivery of SOCS3 via EVs represents a promising avenue for aGVHD prophylaxis, with great potential to improve allo-HSCT outcomes.

2026-09-11 | MTBLS15633 | MetaboLights

Prevention of acute graft-versus-host disease via single-dose administration of bioengineered extracellular vesicles [16S rRNA-seq]

2026-09-13 | GSE347067 | GEO

A clinical trial of Vedolizumab vs. placebo (dummy drug) for the prevention of intestinal Acute Graft Versus Host Disease (aGvHD), in patients undergoing allo-HSCT for a hematologic malignancy, (cancers that affect the blood and/or lymphatic system).

Project description:Main Objective: To evaluate the efficacy of vedolizumab when added to background aGvHD prophylaxis regimen compared to placebo and background aGvHD prophylaxis regimen on intestinal aGvHD-free survival by Day +180 in subjects who receive allo-HSCT as treatment for a hematologic malignancy or myeloproliferative disorder. Primary end point(s): The primary endpoint is intestinal aGvHD-free survival by Day +180 after allo HSCT. Intestinal aGvHD is defined as Stage 1-4 intestinal involvement per Acute Graft versus-Host Disease Clinical Stage criteria.

| 2554383 | ecrin-mdr-crc

Circulating lymphoid committed progenitors after allogeneic stem cell transplantation in humans

Project description:Lymphoid committed CD34+lin-CD10+CD24- progenitors undergo a rebound at month 3 after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the absence of acute graft-versus-host disease (aGVHD). Here, we analyzed transcriptional programs of cell-sorted circulating lymphoid committed progenitors and CD34+Lin-CD10- non lymphoid progenitors in 11 allo-HSCT patients having (n=5) or not developed (n=6) grade 2 or 3 aGVHD and in 7 age-matched healthy donors. Major deregulated pathways included protein synthesis, energy production, cell cycle regulation and cytoskeleton organization. Notably, genes from protein biogenesis, translation machinery and cell cycle (CDK6) were over-expressed in progenitors from patients in the absence of aGVHD compared with healthy donors and patients affected by aGVHD. Expression of many genes from the mitochondrial oxidative phosphorylation metabolic pathway leading to ATP production were more specifically increased in lymphoid committed progenitors in absence of aGVHD. This was also the case for genes involved in cell mobilization such as those regulating Rho GTPases activity. In all, we show that circulating lymphoid committed progenitors undergo profound changes in metabolism favoring cell proliferation, energy production and cell mobilization after allo-HSCT in humans. These mechanisms are abolished in case of aGVHD or its treatment, indicating a persistent cell-intrinsic defect after exit from bone marrow.

2018-11-14 | GSE75344 | GEO

Multiomic Single Cell Evaluation Reveals Inflammatory Cytokines Affect Innate Lymphoid Cell Fate After Allogeneic Stem Cell Transplantation [ChIP-Seq]

Project description:Type II innate lymphoid cells (ILC2s) maintain homeostasis and barrier integrity in mucosal tissues. Previous work has shown that in mice and humans, ILC2s fail to reconstitute after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Determining the mechanisms involved in their impaired reconstitution could improve transplant outcomes. By integrating chromatin and transcriptomic analysis of marked, transplanted ILC2s at the single cell level, we identify a previously unreported population of converted ILC1-like cells in the small intestine post-transplant. Exposure of ILC2s to proinflammatory cytokines in vitro results in a mixed ILC1-ILC2 phenotype but was able to convert only an extremely small population of ILC2s to ILC1s as observed in vivo. Whereas ILC2s protected against acute graft-versus-host disease (aGVHD) mediated-morbidity and mortality, infusion of proinflammatory cytokine-exposed ILC2s accelerated aGvHD. Finally, circulating peripheral blood mononuclear cells from patients with aGvHD have an altered ILC2-associated chromatin landscape compared to transplanted controls. These data demonstrate, for the first time, that ILC2s fail to repopulate their protective niche after allo-HSCT in part due to conversion to a pro-pathogenic population marked by an ILC1-like chromatin state, providing novel insights into the contribution of ILC plasticity to aGvHD pathogenesis after allo-HSCT.

2023-09-14 | GSE232000 | GEO

Functional Transition of CD11b+CD33+HLA-DR-/lowCD14- G-MDSC: Immunostimulation to Immunosuppression Post Allo-HSCT

Project description:The prediction of acute graft-versus-host disease (aGvHD) post allogeneic hematopoietic stem cell transplantation (allo-HSCT) is critical for treatment decisions. The granulocytic myeloid-derived suppressor cells (G-MDSCs) show a fast recovery post-transplantation and constituted the major part of peripheral blood in the early phase after allo-HSCT. These cells were previously believed to exhibit immunosuppressive properties. However, they also promote inflammation under specific conditions. Thus, we conducted a comprehensive study of G-MDSCs from 82 patients after allo-HSCT within 90 days to elucidate the role of them in post-transplantation immunity. Strikingly, our results showed that G-MDSCs promoted inflammation in the early-stage, by facilitating cytokine secretion and proliferation of T cells, as well as their differentiation into pro-inflammatory T helper subsets. At day 28, patients with a higher number of G-MDSCs exhibited an increased risk of developing aGvHD. Besides, adoptive transfer of G-MDSCs from patients into humanized mice exacerbated aGvHD. However, at day 90, G-MDSCs showed immunosuppressive features, characterized by upregulated expression of indoleamine 2,3-dioxygenase gene and interleukin-10 secretion, coupled with the inhibition of T cell proliferation. Furthermore, transcriptional analysis of G-MDSCs at day 28 and day 90 revealed that a total of 1445 genes were differentially expressed. Genes linked to the endoplasmic reticulum stress were upregulated in patients without aGvHD. After the genetic overlap analysis, DERL1 may be the hub-gene. Our findings elucidate the alteration in the immune characteristics of G-MDSCs within the first 90 days post allo-HSCT. Moreover, the quantity of G-MDSCs at day 28 could serve as a predictive indicator for aGvHD.

2024-06-25 | GSE260477 | GEO

CD70 identifies donor derived alloreactive T cells in severe acute Graft vs Host Disease post allogeneic SCT

Project description:Graft-versus-host disease (GvHD) remains a major challenge post allogeneic hematopoietic stem cell transplantation (allo-HSCT) and understanding its immunopathology is crucial for effective therapeutic intervention. Here we investigated the significance of CD70, a co-stimulatory molecule, in the context of aGvHD. CD70 was found to be transiently expressed on activated T cells during early immune reconstitution post-transplantation but persisted longer in aGvHD. Our findings illustrate that CD70+ T cells are characterized by upregulated activation receptors and enhanced cytokine production, while displaying signs of exhaustion. Remarkably, CD70+ T cells expressed chemokine receptors CCR4 and CCR6 and were actively recruited to inflamed tissues, implicating them in aGvHD pathogenesis. The chromatin at transcription factor MGA and NFAT5 loci was found to be selectively altered upon allo-antigenic stimulation in CD70+ T cells ex-vivo. Gene transcriptions of Toll-like receptors and MAPK signalling pathway were also found to differ in CD70+ and CD70- T cells of aGvHD patients. Insights into the clonality and antigen specificity of CD70+ T cell populations revealed potential novel antigenic targets. Further blocking CD70 in allogeneic T cells from aGvHD patients primed with autologous antigen presenting cells prior to HSCT demonstrated that anti-CD70 antibody reduced T cell proliferation and cytokine production. These findings implicate CD70 as a potential therapeutic target to modulate T cell responses and mitigate aGvHD. Targeting the CD70-CD27 co-stimulation pathway holds promise for prophylactic treatment.

2024-10-02 | GSE247452 | GEO

Single-cell transcriptome analysis reveals atypical monocytes circulating ahead of acute graft-versus-host disease clinical onset

Project description:Acute graft-versus-host disease (aGVHD) represents the rejection of the skin, gut and liver tissues of the recipient of an allogenic hematopoietic stem cell transplantation (HSCT) by the donor T-cells. The onset of aGVHD is often rapid and its evolution unpredictable. We undertook the single-cell RNA sequencing of peripheral blood mononuclear cells (PBMCs) collected before aGVHD clinical onset in three patients and at aGVHD diagnosis in one, using four HSCT recipients who remained free of aGVHD as controls. This analysis unveiled the presence in the circulation of particular subpopulations of monocytes and cytotoxic T cells (CTLs) in pre-aGVHD samples up to 18 days before clinical disease. These pre-aGVHD monocytes were characterized by an upregulation of the M2 polarity marker CD163, and the transmembrane protein SIGLEC1/CD169, while their CTL counterparts stood out for the upregulation of the CXCL10 receptor CXCR3 and the antigenic stimulation marker CD70. The occurrence of CD163/CD169-co-expressing monocytes upstream of aGVHD onset was validated using RNAseq data from an independent cohort and by flow cytometry of blood samples. These findings point to potential early diagnostic tools and preventive therapeutic strategies for aGVHD.

2025-07-07 | GSE269338 | 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

Transcriptional analysis of beta-catenin overexpressing T cells

Project description:Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the most widely applied forms of adaptive immunotherapy. Both the detrimental graft-versus-host disease (GVHD) and the beneficial graft-versus-leukemia (GVL) effects occurring after allo-HSCT are largely mediated by alloantigen-reactive donor T cells in the graft. Separating GVHD from GVL effects is a formidable challenge, and a greater understanding of donor T cell biology is required to accomplish the uncoupling of GVHD from GVL. Here, we tested a novel mouse model of transgenic over-expression of human β-catenin (Cat-Tg) in an allo-HSCT model. Our data show that T cells from Cat-Tg mice did not cause GVHD. Surprisingly, Cat-Tg T cells maintained the GVL effect. Donor T cells from Cat-Tg mice exhibited significantly lower inflammatory cytokine production and reduced donor T cell proliferation, while upregulating cytotoxic mediators that resulted in enhanced cytotoxicity. RNA sequencing data revealed changes in the expression of 1169 genes for CD4, and 1006 genes for CD8+T cells involved in essential aspects of immune response and GVHD pathophysiology. Transgenic over-expression of human β-catenin primarily affects CD8+ T cell phenotype. Altogether, our data suggest that β-catenin is a druggable target for developing therapeutic strategies to reduce GVHD while preserving the beneficial GVL effects following allo-HSCT treatment

2021-08-01 | GSE180808 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data