The Macrophage Landscape Across the Lifespan of a Human Cardiac Allograft
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE225652 | GEO | 2024/01/17
REPOSITORIES: GEO
Similar Datasets
Project description:C57/BL6 to C57/BL6; Balb/c to C57/BL6; Balb/c to C57/BL6 with anti CD80/86 mAb; Identificaton of gene expression profile in tolerizing murine cardiac allograft by co-stimulatory blockade. The induction of specific tolerance would be the ultimate achievement in transplant immunology, but the precise mechanisms of immunological tolerance remain largely unknown. Here, we investigated global gene expression analysis in tolerizing murine cardiac allografts by means of oligonucleotide microarrays. Tolerance induction was achieved in cardiac allografts from BALB/c to C57BL/6 mice by daily intraperitoneal injection of anti-CD80 and CD86 mAbs. Comparative analysis revealed 64 genes to be induced more extensively in the tolerizing than in the syngeneic isografts, and 16 genes than in the rejecting allografts. Two genes were specifically upregulated in the tolerizing allografts. In the tolerizing allografts there were induced marked expressions of a number of genes for proinflammatory factors, including interferon-gamma inducible cytokines and chemokines, as well as apoptosis-related genes which were also upregulated in the rejecting allografts. Moreover, these gene expression patterns continued to be upregulated more than 70 days post transplant. These results provide evidence that immunological tolerance can be induced and maintained in the presence of prominent proinflammatory gene expression in vivo.
2007-12-15 | E-GEOD-582 | biostudies-arrayexpress
Project description:Transcriptome analyses of organ transplants have until now usually focused on whole tissue samples containing activation profiles from different cell populations. Here, we enriched endothelial cells from rat cardiac allografts and isografts, establishing their activation profile at baseline and on day 2, 3 and 4 after transplantation. Modulated transcripts were assigned to three categories based on their regulation profile in allografts and isografts. Categories A and B contained the majority of transcripts and showed similar regulation in both graft types, appearing to represent responses to surgical trauma. By contrast, category C contained transcripts that were partly allograft-specific and to a large extent associated with interferon-ï§-responsiveness. Several transcripts were verified by immunohistochemical analysis of graft lesions, among them the matricellular protein periostin which was one of the most highly upregulated transcripts but has not been associated with transplantation previously. In conclusion, the majority of the differentially expressed genes in graft endothelial cells are affected by the transplantation procedure whereas relatively few are associated with allograft rejection. Endothelial cells were enriched from control/non-transplanted hearts and from allografts (DA to Lewis) and isografts (Lewis to Lewis) harvested at day 2, 3 and 4 after transplantation. Three biological replicates from each time point and graft type were analyzed (a total of 24 arrays). Leukocytes were enriched from allografts at day 2 (n=1), day 3 (n=2) and day 4 (n=1) after transplantation.
2010-07-29 | E-GEOD-16695 | biostudies-arrayexpress
Project description:Cardiac allograft rejection remains a significant clinical problem in the early phase after heart transplantation and requires frequent surveillance with endomyocardial biopsy. Endomyocardial tissue samples were obtained in connection with clinical biopsies from twenty consecutive heart transplant patients followed for six months. A rejection episode was observed in 14 patients and biopsies obtained before, during and after the episode were identified. Endomyocardial RNA, from three patients, matching these three points in time were analysed with DNA microarray. Keywords: time course
2006-03-02 | GSE4315 | GEO
Project description:The molecular basis of calcineurin inhibitor toxicity (CNIT) in kidney transplantation (KT) and its contribution to chronic allograft dysfunction (CAD) with interstitial fibrosis (IF) and tubular atrophy (TA) were evaluated. Molecular signatures characterizing CNIT samples were identified. The recognized CNIT gene signature was most common in patients with decreased graft function and histological evidence of IF/TA. To test CNIT contribution to CAD progression, kidney biopsies from transplant recipients with histological diagnosis of CNIT (n=14), acute rejection (ACR, n=13), and CAD with IF/TA (n=10), including 18 Normal allografts, were analyzed using gene expression microarrays.
2014-06-01 | E-GEOD-53605 | biostudies-arrayexpress
Project description:Erythropoietin (EPO) has multiple functions beyond stimulating erythrocytosis, including modulation of T cell immunity. Effects EPO in transplantation and associated mechanisms remain incompletely understood. We analyzed outcomes and performed cellular and molecular mechanistic assessments in murine wild type (WT) and conditional EPO receptor (EPOR) knockout recipients of cardiac allografts. In translational studies, we tested EPO’s effects in a non-human primate system.
2023-03-01 | GSE199270 | GEO
Project description:Cardiac allograft rejection remains a significant clinical problem in the early phase after heart transplantation and requires frequent surveillance with endomyocardial biopsy. Endomyocardial tissue samples were obtained in connection with clinical biopsies from twenty consecutive heart transplant patients followed for six months. A rejection episode was observed in 14 patients and biopsies obtained before, during and after the episode were identified. Endomyocardial RNA, from three patients, matching these three points in time were analysed with DNA microarray. Experiment Overall Design: Three subjects (subject number 1,8 and 12) Experiment Overall Design: Three timepoints (Before, during and after an rejection episode)
2007-12-12 | E-GEOD-4315 | biostudies-arrayexpress
Project description:The Australian Chronic Allograft Dysfunction (AUSCAD) study is an ongoing single centre cohort study at Westmead hospital in Australia. In this section of the study, we aimed to identify biomarkers for chronic allograft dysfunction in kidney transplant recipients. Our study recruited 136 patients, each having protocol renal allograft biopsies taken pre transplantation.
2024-04-05 | GSE261240 | GEO
Project description:Background: While heart transplantation is the standard treatment for heart failure, both acute and chronic transplant rejection frequently occur. Since the modulation of protein phosphatase PP2A activity is critical for tissue and organ homeostasis under physiological and pathophysiological conditions, PP2A may also affect the ability to tolerate transplanted organs. Here we demonstrate that administration of a novel class of small molecule activators of PP2A (SMAPs) prolonged cardiac allograft survival in a mouse heterotopic heart transplantation model. Mechanistically, SMAPs effectively suppressed the inflammatory immune response while increasing Treg population in the allografts, findings corroborated by functional analysis of RNAseq data derived from Tregs of treated splenic tissue. Importantly, SMAPs further prolonged CTLA4-Ig (an immunosuppressive agent utilized in organ transplantation)-induced cardiac rejection tolerance and extended allograft survival. SMAPs also strongly mitigated cardiac allograft vasculopathy as evidenced by a marked reduction of neointimal hyperplasia and smooth muscle cell proliferation. Mechanistic studies implicate SMAPs elicited suppression of MEK/ERK pathways as a unifying mechanism for the aforementioned effects in Tregs and SMCs. These findings highlight the potential of PP2A activation in improving alloengraftment in heart transplantation and add knowledge to the phosphatase driven regulation of the immune system in the context of organ transplantation.
2023-07-20 | GSE236206 | GEO
Project description:Genomic Analysis of more than 400 patients from multi-center transplant programs and clinical trials provides a non-invasive QPCR based gene expression test for operational renal allograft tolerance 3 group comparison of blood from TOL, CAN and Non-transplant healthy controls (HD) allografts. Biological replicates: 16 TOL, 10 CAN and 5 HC
2015-01-08 | E-GEOD-45218 | biostudies-arrayexpress
Project description:The Australian Chronic Allograft Dysfunction (AUSCAD) study is an ongoing single centre cohort study at Westmead hospital in Australia. In this section of the study, we aimed to identify biomarkers for allograft rejection in kidney transplant recipients, 3-months after their transplant. Our study recruited 123 patients, each having protocol renal allograft biopsies taken 3-months post transplantation.
2024-04-05 | GSE261892 | GEO