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FRCs promote Treg function in acute graft-versus-host disease (aGvHD)

ABSTRACT: Knockout of MHC class II on Ccl19 expressing fibroblastic reticular cells results in the hyper-activation of allogenic CD4+ T cells in the effoctor phase of aGvHD, due to the dyregulation of regulatory T cells (Tregs).

ORGANISM(S): Mus musculus

PROVIDER: GSE168114 | GEO | 2021/03/03

REPOSITORIES: GEO

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FRCs promote Treg function in acute graft-versus-host disease (aGvHD)

Project description:FRCs promote Treg function in acute graft-versus-host disease (aGvHD)

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Project description:Allogeneic peripheral blood stem cell transplantation (PBSCT) is indicated for the treatment of high-risk hematological malignancies, and in some cases is a cancer cure. A major complication associated with PBSCT (affecting approximately half of recipients) is acute graft-versus-host disease (aGVHD). In aGVHD, alloreactive donor T cells becoming activated by host dendritic cells (DC) in response to pro-inflammatory cytokines released during the conditioning regimen. The result is donor-derived CD4+ T helper-type 1 (Th1) cells maturing and subsequently imposing cytolytic effector responses on host tissues, resulting in multi-organ damage. Despite this well-defined pathophysiological mechanism, there are no definitive markers for predicting aGVHD development or progression to clinically advanced stages. In the current study, we enrolled 8 PBSCT recipients in an IRB-approved study and collected peripheral blood at the time to engraftment. Of these, four patients developed aGVHD within 5-10 days post transplant. The remaining four patients were aGVHD-free. Using total RNA collected from whole blood leukocytes, we analyzed each recipientâs gene expression profile on Affymetrix GeneChip Human Genome U133 Plus 2.0 microarrays. Experiment Overall Design: Samples 1-4 are control patients; 5-8 are aGVHD patients. Peripheral blood was collected at engraftment and used for microarray analysis. In analysing the data, the type of transplant (MUD, related) was used as a covariate to assess if there were significant changes in gene expression between the control (1-4) and aGVHD (5-8) groups, based on a 10% FDR with a pooled error estimate.

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Plasma in patients with acute myeloid leukemia (AML) with acute graft versus host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation vs Plasma in patients with AML without aGVHD

Project description:Comparing between plasma cytokine proteins on AML patients with or without aGVHD Comparing between plasma cytokine proteins on AML patients with or without aGVHD after allogeneic hematopoietic stem cell transplantation, Day+14

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Transcriptional profiling of PBMC from patients with aGvHD and patients without aGvHD after alloHSCT

Project description:The goal of this study are to identify critical biomarkers distinguishing alloHSCT recipients with aGvHD from alloHSCT recipients without aGvHD in two separate cohorts. Total RNA was isolated from the peripheral blood mononucleated cells and then quantified on a Bioanalyzer. Whole transcriptome sequencing libraries (3 pairs of aGvHD and controls, 6 libraries in total) were prepared following the manufacturer’s instructions for the Whole Transcriptome Sample Prep Kit (Illumina) by GENEWIZ Company. 1148 presented significant alterations in cases with aGvHD (t test, FDR corrected P < 0.05, |fold change|>1.5). Transcriptomic pathway analysis showed that the GPL metabolism pathway was one of the most significant pathways with Bonferroni correction P value (Q value) less than 0.001, indicating that it was a critical pathway related to the development of aGvHD.

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Project description:Lymph node (LN) stromal cells, particularly fibroblastic reticular cells (FRCs), provide critical structural support and regulate immunity, tolerance and transport properties of LNs. In many tumors, LN metastasis is predictive of poor prognosis, however, stromal contribution to the evolving microenvironment of tumor draining LNs (TDLN) remains poorly understood. Here we present comparative transcriptional data of resting and TDLN FRCs after different time points of tumor drainage. FRCs were isolated from lymph nodes and FACS sorted based on the expression of CD45-, CD31- and PDPN+

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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).

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Single-cell RNA sequencing of niche cells from WT, BMT and aGVHD mice

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