Deficiency of neutrophil high-mobility group box-1 in liver transplant recipients exacerbates early allograft injury in mice
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ABSTRACT:
PROVIDER: PRJNA933932 | ENA |
REPOSITORIES: ENA
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Project description:To investigate the role of recipient neutrophil intracellular HMGB1 in early allograft injury after liver transplant. Using a mouse orthotopic liver transplant model, as well as LPS injection, we found that neutrophils significantly infiltrate the liver after liver transplant and LPS challenge. Deficiency of neutrophil HMGB1 enhances their activation, boosts their pro-oxidant and pro-inflammatory phenotype, and hinders biosynthesis and metabolism of inositol polyphosphates. Overall, these events exacerbate early allograft injury after liver transplant.
2023-07-27 | GSE225106 | GEO
Project description:This experiment compare the transcriptional profile of CD8+CD45RClow Tregs from naive untreated rats compared to CD40Ig-treated tolerant allograft recipients.
2015-11-30 | E-MTAB-3535 | biostudies-arrayexpress
Project description:Transcriptomic analyses reveal regional signatures in lung allograft recipients
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Project description:Background and objective: Long term outcomes of allograft recipients are compromised by the development of chronic lung allograft dysfunction (CLAD) or bronchiolitis obliterans syndrome (BOS) which initiates in the lung periphery. We established baseline transcriptomic profiles of both the large and small airway epithelial cells (referred as LAEC and SAEC, respectively) to identify regional differences irrespective of initiating disease. Methods: We obtained matched primary LAEC and SAEC from lung allograft recipients (n=4, 42.5±4.2 years) and established primary cultures. Bulk RNA sequencing was performed to determine differentially expressed genes. Results: We observed differences in the transcriptional program between LAEC and SAEC Transcription factors (TF) were ranked within the top ten differentially regulated genes. The most abundant TF families included C2H2-ZF, homeobox and bHLH. Upstream regulator analyses identified homeobox genes being significantly in LAEC. Protein-protein interaction network analysis emphasised the role of TFs (ISL1, MSX1, HOXA1, GATA6, ZNF423) in airway modulation. Additionally, functional enrichment analysis revealed the activation of chemotaxis, metalloendipeptidase/metallopeptidase activity and pro-inflammatory signatures (IL17 signalling and RAGE), in LAEC, while SAEC were characterised by elevated expression of surfactant metabolism related genes. Moreover, alveolar and club cells-related genes were expressed in SAEC, suggesting a lower airway-specific signature. Conclusion: Our analysis shows robust transcriptional differences between LAEC and SAEC. We suggest a potential role for homeobox TF family as well as the activation of the immune system in the biology of LAEC. Conversely, we observed an alveoli-like transcriptional signature in SAEC, including gas-exchange signals and surfactant metabolism; pathways involved in lung homeostasis.
2022-10-01 | GSE214434 | GEO
Project description:Purpose: Determine the mechanism of high mobility group box 1 (HMGB1)-induced signaling in melanocytes. Method: Primary human epidermal melanocytes were treated with HMGB1 (1 μg/ml) and incubated for 24 h. Total RNA (500 ng) from melanocytes were extracted and subjected to library synthesis. Results: HMGB1-treated melanocytes exhibited upregulation of cell death and type 1 interferon-related genes. Conclusion: HMGB1-induced melanocyte signaling was well evaluated using RNA sequencing.
2023-07-28 | GSE216423 | GEO
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.
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Project description:RNA sequencing of high mobility group box 1-treated melanocytes [hmgb1]
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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
Project description:Kidney transplantation is a preeminent treatment for end-stage renal disease . The application of immunosuppressants is needed for kidney recipients to avoid allograft rejection but increase the risk of infection, and balance between rejection and infection is an important in clinical to reach the immune accommodation. Here, we use single-cell RNA sequencing to fully assess the immune status of peripheral mononuclear cells in kidney recipients. and compared the differences between kidney recipients and healthy people to describe the characteristics of the immune accommodation of kidney recipients. We found a novel B cell subset (CD19+IGKC+IGLC3lowTCL1A-CD127+) of renal transplant recipients with accommodation was significantly lower than that of healthy people and verified by flow cytometry. which may have potential regulatory potential. Furthermore, we found that IL32 may increase the expression of CD19+IGKC+IGLC3lowTCL1A-CD127+ Bcells. In summary, we found that the CD19+IGKC+IGLC3lowTCL1A-CD127+B subgroup with immunomodulatory potential is inhibited in kidney recipients with accommodation state, and IL-32 has therapeutic potential for this.
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Project description:Steroid-refractory acute rejection is a risk factor for inferior renal allograft outcome. We aimed to gain insight into the mechanisms underlying steroid resistance by identifying novel molecular markers of steroid-refractory acute rejection. Eighty-three kidney transplant recipients (1995-2005), who were treated with methylprednisolone during a first acute rejection episode, were included in this study. Gene expression patterns were investigated in a discovery cohort of 36 acute rejection biopsies, and verified in a validation cohort of 47 acute rejection biopsies. In the discovery set, expression of metallothioneins (MT) was significantly (P<0.000001) associated with decreased response to steroid treatment. Multivariate analysis resulted in a predictive model containing MT-1 as an independent covariate (AUC=0.88, P<0.0000001). In the validation set, MT-1 expression was also significantly associated with steroid resistance (P=0.029). Metallothionein expression was detected in macrophages and tubular epithelial cells. Parallel to the findings in patients, in vitro experiments of peripheral blood mononuclear cells from 11 donors showed that non-response to methylprednisolone treatment is related to highly elevated MT levels. High expression of metallothioneins in renal allografts is associated with resistance to steroid treatment. Metallothioneins regulate intracellular concentrations of zinc, through which they may diminish the zinc-requiring anti-inflammatory effect of the glucocorticoid receptor. Transcriptional profiles of 40 renal allograft biopsy samples were analyzed using Illumina HumanRef-8 v3.0 BeadChips (Illumina, San Diego, CA). Expression profiles were investigated in total RNA isolated from biopsy samples of 18 patients with steroid responsive acute rejection and 18 patients with steroid resistant acute rejection. Four biopsies, taken during acute decrease of graft function but with no histomorphologic indication of rejection, were included as controls.
2013-05-21 | E-GEOD-47097 | biostudies-arrayexpress