Dressel, Ralf

[["dc.bibliographiccitation.artnumber","380"],["dc.bibliographiccitation.journal","Frontiers in Immunology"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Gam, Rihab"],["dc.contributor.author","Shah, Pranali"],["dc.contributor.author","Crossland, Rachel E."],["dc.contributor.author","Norden, Jean"],["dc.contributor.author","Dickinson, Anne M."],["dc.contributor.author","Dressel, Ralf"],["dc.date.accessioned","2019-07-09T11:43:18Z"],["dc.date.available","2019-07-09T11:43:18Z"],["dc.date.issued","2017"],["dc.description.abstract","The outcome of hematopoietic stem cell transplantation (HSCT) is controlled by genetic factors among which the leukocyte antigen human leukocyte antigen (HLA) matching is most important. In addition, minor histocompatibility antigens and non-HLA gene polymorphisms in genes controlling immune responses are known to contribute to the risks associated with HSCT. Besides single-nucleotide polymorphisms (SNPs) in protein coding genes, SNPs in regulatory elements such as microRNAs (miRNAs) contribute to these genetic risks. However, genetic risks require for their realization the expression of the respective gene or miRNA. Thus, gene and miRNA expression studies may help to identify genes and SNPs that indeed affect the outcome of HSCT. In this review, we summarize gene expression profiling studies that were performed in recent years in both patients and animal models to identify genes regulated during HSCT. We discuss SNP– mRNA–miRNA regulatory networks and their contribution to the risks associated with HSCT in specific examples, including forkheadbox protein 3 and regulatory T cells, the role of the miR-155 and miR-146a regulatory network for graft-versus-host disease, and the function of MICA and its receptor NKG2D for the outcome of HSCT. These examples demonstrate how SNPs affect expression or function of proteins that modulate the alloimmune response and influence the outcome of HSCT. Specific miRNAs targeting these genes and directly affecting expression of mRNAs are identified. It might be valuable in the future to determine SNPs and to analyze miRNA and mRNA expression in parallel in cohorts of HSCT patients to further elucidate genetic risks of HSCT."],["dc.identifier.doi","10.3389/fimmu.2017.00380"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14421"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58858"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation","info:eu-repo/grantAgreement/EC/FP7/315963/EU/Improving HSCT By Validation Of Biomarkers & Development Of Novel Cellular Therapies/CELLEUROPE"],["dc.relation.issn","1664-3224"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Genetic Association of Hematopoietic Stem Cell Transplantation Outcome beyond Histocompatibility Genes"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","361"],["dc.bibliographiccitation.journal","Frontiers in Immunology"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Jalapothu, Dasaradha"],["dc.contributor.author","Boieri, Margherita"],["dc.contributor.author","Crossland, Rachel E."],["dc.contributor.author","Shah, Pranali"],["dc.contributor.author","Butt, Isha A."],["dc.contributor.author","Norden, Jean"],["dc.contributor.author","Dressel, Ralf"],["dc.contributor.author","Dickinson, Anne M."],["dc.contributor.author","Inngjerdingen, Marit"],["dc.date.accessioned","2018-11-07T10:08:30Z"],["dc.date.available","2018-11-07T10:08:30Z"],["dc.date.issued","2016"],["dc.description.abstract","MicroRNAs (miRNA) have emerged as central regulators of diverse biological processes and contribute to driving pathology in several diseases. Acute graft-versus-host disease (aGvHD) represents a major complication after allogeneic hematopoietic stem cell transplantation, caused by alloreactive donor T cells attacking host tissues leading to inflammation and tissue destruction. Changes in miRNA expression patterns occur during aGvHD, and we hypothesized that we could identify miRNA signatures in target tissues of aGvHD that may potentially help understand the underlying molecular pathology of the disease. We utilized a rat model of aGvHD with transplantation of fully MHC-mismatched T cell depleted bone marrow, followed by infusion of donor T cells. The expression pattern of 423 rat miRNAs was investigated in skin, gut, and lung tissues and intestinal T cells with the NanoString hybridization platform, in combination with validation by quantitative PCR. MHC-matched transplanted rats were included as controls. In the skin, upregulation of miR-34b and downregulation of miR-326 was observed, while in the intestines, we detected downregulation of miR-743b and a trend toward downregulation of miR-345-5p. Thus, tissue-specific expression patterns of miRNAs were observed. Neither miR-326 nor miR-743b has previously been associated with aGvHD. Moreover, we identified upregulation of miR-146a and miR-155 in skin tissue of rats suffering from aGvHD. Analysis of intestinal T cells indicated 23 miRNAs differentially regulated between aGvHD and controls. Two of these miRNAs were differentially expressed either in skin (miR-326) or in intestinal (miR-345-5p) tissue. Comparison of intestinal and peripheral blood T cells indicated common dysregulated expression of miR-99a, miR-223, miR-326, and miR-345-5p. Analysis of predicted gene targets for these miRNAs indicated potential targeting of an inflammatory network both in skin and in the intestines that may further regulate inflammatory cytokine production. In conclusion, comprehensive miRNA profiling in rats suffering from aGvHD demonstrate tissue-specific differences in the expression patterns of miRNA that may not be detected by profiling of peripheral blood T cells alone. These tissue-specific miRNAs may contribute to distinct pathologic mechanisms and could represent potential targets for therapy."],["dc.description.sponsorship","European Union [FP7-PEOPLE-2012-ITN-315963]"],["dc.identifier.doi","10.3389/fimmu.2016.00361"],["dc.identifier.isi","000383320200001"],["dc.identifier.pmid","27695455"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13746"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/39474"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Frontiers Media Sa"],["dc.relation.issn","1664-3224"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Tissue-specific expression Patterns of Microrna during acute graft-versus-host Disease in the rat"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e16582"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Novota, Peter"],["dc.contributor.author","Zinocker, Severin"],["dc.contributor.author","Norden, Jean"],["dc.contributor.author","Wang, X."],["dc.contributor.author","Sviland, Lisbet"],["dc.contributor.author","Opitz, Lennart"],["dc.contributor.author","Salinas-Riester, Gabriela"],["dc.contributor.author","Rolstad, Bent"],["dc.contributor.author","Dickinson, Anne M."],["dc.contributor.author","Walter, Lutz"],["dc.contributor.author","Dressel, Ralf"],["dc.date.accessioned","2018-11-07T09:00:02Z"],["dc.date.available","2018-11-07T09:00:02Z"],["dc.date.issued","2011"],["dc.description.abstract","Background: The major histocompatibility complex (MHC) is the most important genomic region that contributes to the risk of graft versus host disease (GVHD) after haematopoietic stem cell transplantation. Matching of MHC class I and II genes is essential for the success of transplantation. However, the MHC contains additional genes that also contribute to the risk of developing acute GVHD. It is difficult to identify these genes by genetic association studies alone due to linkage disequilibrium in this region. Therefore, we aimed to identify MHC genes and other genes involved in the pathophysiology of GVHD by mRNA expression profiling. Methodology/Principal Findings: To reduce the complexity of the task, we used genetically well-defined rat inbred strains and a rat skin explant assay, an in-vitro-model of the graft versus host reaction (GVHR), to analyze the expression of MHC, natural killer complex (NKC), and other genes in cutaneous GVHR. We observed a statistically significant and strong up or down regulation of 11 MHC, 6 NKC, and 168 genes encoded in other genomic regions, i.e. 4.9%, 14.0%, and 2.6% of the tested genes respectively. The regulation of 7 selected MHC and 3 NKC genes was confirmed by quantitative real-time PCR and in independent skin explant assays. In addition, similar regulations of most of the selected genes were observed in GVHD-affected skin lesions of transplanted rats and in human skin explant assays. Conclusions/Significance: We identified rat and human MHC and NKC genes that are regulated during GVHR in skin explant assays and could therefore serve as biomarkers for GVHD. Several of the respective human genes, including HLA-DMB, C2, AIF1, SPR1, UBD, and OLR1, are polymorphic. These candidates may therefore contribute to the genetic risk of GVHD in patients."],["dc.identifier.doi","10.1371/journal.pone.0016582"],["dc.identifier.isi","000286664100046"],["dc.identifier.pmid","21305040"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8196"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/24049"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Public Library Science"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 2.5"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.5"],["dc.title","Expression Profiling of Major Histocompatibility and Natural Killer Complex Genes Reveals Candidates for Controlling Risk of Graft versus Host Disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","355"],["dc.bibliographiccitation.journal","Frontiers in Immunology"],["dc.bibliographiccitation.volume","3"],["dc.contributor.author","Zinocker, Severin"],["dc.contributor.author","Dressel, Ralf"],["dc.contributor.author","Wang, X."],["dc.contributor.author","Dickinson, Anne M."],["dc.contributor.author","Rolstad, Bent"],["dc.date.accessioned","2018-11-07T09:16:16Z"],["dc.date.available","2018-11-07T09:16:16Z"],["dc.date.issued","2012"],["dc.description.abstract","Allogeneic hematopoietic cell transplantation (alloHCT) extends the lives of thousands of patients who would otherwise succumb to hematopoietic malignancies such as leukemias and lymphomas, aplastic anemia, and disorders of the immune system. In alloHCT, different immune cell types mediate beneficial graft-versus-tumor (GvT) effects, regulate detrimental graft-versus-host disease (GvHD), and are required for protection against infections. Today, the \"good\" (GvT effector cells and memory cells conferring protection) cannot be easily separated from the \"bad\" (GvHD-causing cells), and alloHCT remains a hazardous medical modality. The transplantation of hematopoietic stem cells into an immunosuppressed patient creates a delicate environment for the reconstitution of donor blood and immune cells in co-existence with host cells. Immunological reconstitution determines to a large extent the immune status of the allo-transplanted host against infections and the recurrence of cancer, and is critical for long-term protection and survival after clinical alloHCT. Animal models continue to be extremely valuable experimental tools that widen our understanding of, for example, the dynamics of post-transplant hematopoiesis and the complexity of immune reconstitution with multiple ways of interaction between host and donor cells. In this review, we discuss the rat as an experimental model of HCT between allogeneic individuals. We summarize our findings on lymphocyte reconstitution in transplanted rats and illustrate the disease pathology of this particular model. We also introduce the rat skin explant assay, a feasible alternative to in vivo transplantation studies. The skin explant assay can be used to elucidate the biology of graft-versus-host reactions, which are known to have a major impact on immune reconstitution, and to perform genome-wide gene expression studies using controlled combinations of minor and major histocompatibility between the donor and the recipient."],["dc.description.sponsorship","European Union [MRTN-CT-2004-512253, FP7-PEOPLE-2012-ITN-315963]"],["dc.identifier.doi","10.3389/fimmu.2012.00355"],["dc.identifier.isi","000209501300350"],["dc.identifier.pmid","23226148"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/9977"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/27896"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Frontiers Research Foundation"],["dc.relation.issn","1664-3224"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.title","Immune reconstitution and graft-versus-host reactions in rat models of allogeneic hematopoietic cell transplantation"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]