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GSE56017
Homo sapiens
22 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Tolerogenic dendritic cells (tol-DCs) offer a promising therapeutic potential for autoimmune diseases. Tol-DCs have been reported to inhibit immunogenic responses, yet little is known about the mechanisms controlling their tolerogenic status, as well as associated specific markers. Here we show that the anti-inflammatory TAM receptor tyrosine kinase MERTK, is highly expressed on clinical grade dexamethasone-induced human tol-DCs and mediates their tolerogenic effect. Neutralization of MERTK in allogenic mixed lymphocyte reactions as well as autologous DC-T cell cultures leads to increased T cell proliferation and IFN-g production. Additionally, we identify a previously unrecognized non-cell autonomous regulatory function of MERTK expressed on DCs. Recombinant Mer-Fc protein, used to mimic MERTK on DCs, suppresses nave and antigen-specific memory T cell activation. This mechanism is mediated by the neutralization of the MERTK agonist Protein S (PROS1) expressed by T cells. We find that MERTK and PROS1 are expressed in human T cells upon TCR activation and drive an autocrine pro-proliferative mechanism. Collectively, these results suggest that MERTK on tol-DCs directly inhibits T cell activation through the competition for PROS1 interaction with MERTK in the T cells. Targeting MERTK may provide an interesting approach to effectively increase or suppress tolerance for the purpose of immunotherapy.
Publication Title
MERTK as negative regulator of human T cell activation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
Crohn's Disease (CD) is a chronic inflammatory disease of the intestinal tract.
Publication Title
Commensal-Specific CD4(+) Cells From Patients With Crohn's Disease Have a T-Helper 17 Inflammatory Profile.
Sample Metadata Fields
Sex, Age, Disease, Subject
View Samples- Homo sapiens
- 42 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
Treatment of severely refractory Crohns disease (CD) patients remains a clinical challenge. Recent studies show efficacy of autologous hematopoietic stem cell transplant (HSCT) in these severely compromised patients. HSCT is thought to eliminate auto-reactive cells; however the mechanisms are incompletely understood. We followed a group of patients (n=18) receiving autologous HSCT, with 50% of them achieving endoscopic drug-free remission. To elucidate the mechanism driving efficacy we compared the immunological changes induced by HSCT in responders and non-responders.
Publication Title
Differences in peripheral and tissue immune cell populations following hematopoietic stem cell transplantation in Crohn's disease patients.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Time
View Samples- Homo sapiens
- 80 Downloadable Samples
Illumina HiSeq 4000
Description
Treatment of severely refractory Crohn's disease (CD) patients remains a clinical challenge. Recent studies show the efficacy of autologous hematopoietic stem cell transplant (HSCT) in these severely compromised patients. HSCT is thought to eliminate auto-reactive cells; however, no specific studies of immune reconstitution in CD patients are available. We studied a group of CD patients receiving autologous HSCT, with 50% of them achieving endoscopic drug-free remission. To elucidate the mechanism driving efficacy, we studied changes in the immune cell composition in tissue induced by HSCT. Overall design: Biopsy mRNA profiles of 14 CD patients undergoing HSCT were generated by deep sequencing, using HiSeq-4000 platform (Illumina, San Diego, CA).
Publication Title
Differences in Peripheral and Tissue Immune Cell Populations Following Haematopoietic Stem Cell Transplantation in Crohn's Disease Patients.
Sample Metadata Fields
Sex, Specimen part, Disease, Subject
View Samples- Sus scrofa
- 26 Downloadable Samples
- Illumina HiSeq 2000
Description
Identification of genes and causal mutations regulating growth and fatness traits in pig. Overall design: Transcriptome sequencing of 10 liver samples of two groups of divergent pigs for growth and fatness.
Publication Title
Using RNA-Seq SNP data to reveal potential causal mutations related to pig production traits and RNA editing.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Sus scrofa
- 15 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
We studied the influence of the oleic acid content of the diet on adipose tissue transcriptome.
Publication Title
Dietary energy source largely affects tissue fatty acid composition but has minor influence on gene transcription in Iberian pigs.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Sus scrofa
- 26 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
We studied the influence of genetic type (pure Iberian pigs vs crossbred with Duroc) on l.dorsi transcriptome
Publication Title
Longissimus dorsi transcriptome analysis of purebred and crossbred Iberian pigs differing in muscle characteristics.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 24 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Intra-graft expression of genes involved in iron homeostasis predicts the development of operational tolerance in human liver transplantation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 70 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Complications due to long-term administration of immunosuppressive therapy increase the morbidity and mortality of liver transplant recipients. Discontinuation of immunosuppressive drugs in recipients spontaneously developing operational tolerance could substantially lessen this burden. However, this strategy results in the development of rejection in a high proportion of recipients who require lifelong immunosuppression. Thus, there is a need to identify predictive factors of successful drug withdrawal and to define the clinical and histological outcomes of operationally tolerant liver recipients. Methods. We enrolled 102 stable liver transplant recipients in an immunosuppression withdrawal trial in which drugs were gradually discontinued over a 6-9 month period. Patients with stable graft function and no signs of rejection in a liver biopsy conducted 12 months after cessation of immunosuppressive therapy were considered operationally tolerant. Results. Out of the 98 recipients who completed the study, immunosuppression discontinuation was successful in 41 recipients and rejection occurred in 57. Rejection episodes were mild and were resolved in all cases. Development of tolerance was independently associated with time elapsed since transplantation, recipient age, and male gender. No histological damage was apparent in protocol biopsies performed after successful drug withdrawal.
Publication Title
Intra-graft expression of genes involved in iron homeostasis predicts the development of operational tolerance in human liver transplantation.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In clinical organ transplantation complete cessation of immunosuppressive therapy can be successfully accomplished in selected recipients providing a proof-of-principle that allograft tolerance is attainable in humans. The intra-graft molecular pathways associated with human allograft tolerance, however, have not been comprehensively studied before. In this study we analyzed sequential liver tissue samples collected from liver recipients enrolled in a prospective multicenter immunosuppressive withdrawal clinical trial. Tolerant and non-tolerant recipients differed in the intra-graft expression of genes involved in the regulation of iron homeostasis.These results point to a critical role of iron homeostasis in the regulation of intra-graft alloimmune responses in humans and provide a set of novel biomarkers to conduct drug-weaning trials in liver transplantation.
Publication Title
Intra-graft expression of genes involved in iron homeostasis predicts the development of operational tolerance in human liver transplantation.
Sample Metadata Fields
No sample metadata fields
View Samples