Shah, Pranali Nitin

[["dc.bibliographiccitation.artnumber","UNSP 333"],["dc.bibliographiccitation.journal","Frontiers in Immunology"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Boieri, Margherita"],["dc.contributor.author","Shah, Pranali"],["dc.contributor.author","Dressel, Ralf"],["dc.contributor.author","Inngjerdingen, Marit"],["dc.date.accessioned","2018-11-07T10:10:01Z"],["dc.date.available","2018-11-07T10:10:01Z"],["dc.date.issued","2016"],["dc.description.abstract","Bone marrow transplantation (BMT) is the only therapeutic option for many hematological malignancies, but its applicability is limited by life-threatening complications, such as graft-versus-host disease (GvHD). The last decades have seen great advances in the understanding of BMT and its related complications; in particular GvHD. Animal models are beneficial to study complex diseases, as they allow dissecting the contribution of single components in the development of the disease. Most of the current knowledge on the therapeutic mechanisms of BMT derives from studies in animal models. Parallel to BMT, the understanding of the pathophysiology of GvHD, as well as the development of new treatment regimens, has also been supported by studies in animal models. Pre-clinical experimentation is the basis for deep understanding and successful improvements of clinical applications. In this review, we retrace the history of BMT and GvHD by describing how the studies in animal models have paved the way to the many advances in the field. We also describe how animal models contributed to the understanding of GvHD pathophysiology and how they are fundamental for the discovery of new treatments."],["dc.description.sponsorship","European Union grant (CELLEUROPE) [FP7-PEOPLE-2012-ITN-315963]"],["dc.identifier.doi","10.3389/fimmu.2016.00333"],["dc.identifier.isi","000382119100001"],["dc.identifier.pmid","27625651"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13724"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/39772"],["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","The Role of Animal Models in the Study of Hematopoietic Stem Cell Transplantation and GvHD: A Historical Overview"],["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.firstpage","33"],["dc.bibliographiccitation.journal","Experimental Hematology"],["dc.bibliographiccitation.lastpage","45"],["dc.bibliographiccitation.volume","50"],["dc.contributor.author","Boieri, Margherita"],["dc.contributor.author","Shah, Pranali"],["dc.contributor.author","Jalapothu, Dasaradha"],["dc.contributor.author","Zaitseva, Olena"],["dc.contributor.author","Walter, Lutz"],["dc.contributor.author","Rolstad, Bent"],["dc.contributor.author","Naper, Christian"],["dc.contributor.author","Dressel, Ralf"],["dc.contributor.author","Inngjerdingen, Marit"],["dc.date.accessioned","2018-11-07T10:23:07Z"],["dc.date.available","2018-11-07T10:23:07Z"],["dc.date.issued","2017"],["dc.description.abstract","Acute graft-versus-host disease (aGvHD) remains a significant hurdle to successful treatment of many hematological disorders. The disease is caused by infiltration of alloactivated donor T cells primarily into the gastrointestinal tract and skin. Although cytotoxic T cells mediate direct cellular damage, T helper (Th) cells differentially secrete inununoregulatory cytokines. aGvHD is thought to be initiated primarily by Thl cells but a consensus is still lacking regarding the role of Th2 and Th17 cells. The aim of this study was to determine the contribution of distinct T-cell subsets to aGvHD in the rat. aGvHD was induced by transplanting irradiated rats with T-cell depleted major histocompatibility complex-mismatched bone marrow, followed 2 weeks later by donor lymphocyte infusion. Near complete donor T-cell chimerism was achieved in the blood and lymphatic tissues, in contrast to mixed chimerism in the skin and gut. Skin and gut donor T cells were predominantly CD4(+), in contrast to T cells in the blood and lymphatic tissues. Genes associated with Th1 cells were upregulated in gut, liver, lung, and skin tissues affected by aGvHD. Increased serum levels of CXCL10 and IL-18 preceded symptoms of aGvHD, accompanied by increased responsiveness to CXCL10 by blood CD4(+) T cells. No changes in the expression of Th2- or Th17-associated genes were observed, indicating that aGvHD in this rat model is mainly Thl driven. The rat model of aGvHD could be instrumental for further investigations of donor T-cell subsets in the skin and gut and for exploring therapeutic options to ameliorate symptoms of aGvHD. Copyright (C) 2017 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc."],["dc.description.sponsorship","European Union [FP7-PEOPLE-2012-ITN-315963]"],["dc.identifier.doi","10.1016/j.exphem.2017.02.002"],["dc.identifier.isi","000403302300005"],["dc.identifier.pmid","28238806"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42397"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Elsevier Science Inc"],["dc.relation.issn","1873-2399"],["dc.relation.issn","0301-472X"],["dc.title","Rat acute GvHD is Th1 driven and characterized by predominant donor CD4(+) T-cell infiltration of skin and gut"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["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"]]