Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Comparison between syngeneic kidney transplant and a model of allogeneic kidney transplant tolerance induced by anti-classII regimen in the rat

ABSTRACT: The goal is to identify new molecules implicated in tolerance, to determine the implication of these molecules in immune responses to transplantation by gene expression comparison of 27,088 individual rat genes between tolerated kidney allotransplant and syngeneic kidney transplant. In this study 27,088 individual rat genes expression from total mRNA of 3 tolerated allogeneic kidney transplants by anti-classII, were compared to 3 syngeneic kidney transplants at day 100 post transplantation.

ORGANISM(S): Rattus norvegicus

SUBMITTER: Romain Vuillefroy de Silly

PROVIDER: E-GEOD-28474 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Transplant tolerance is associated with reduced expression of cystathionine-γ-lyase that controls IL-12 production by dendritic cells and TH-1 immune responses.

Vuillefroy de Silly Romain R Coulon Flora F Poirier Nicolas N Jovanovic Vojislav V Brouard Sophie S Ferchaud-Roucher Véronique V Blancho Gilles G Vanhove Bernard B

Blood 20120119 11

Antigen-activated T lymphocytes undergo an immune or tolerogeneic response in part according to the activation status of their antigen-presenting cells. However, factors controlling the activation of antigen-presenting cells are not fully understood. In this study, we demonstrate that immune tolerance after organ allotransplantation in the rat is associated with a repressed intragraft expression of several enzymes of the trans-sulfuration pathway, including cystathionine γ-lyase (CSE). The pharm ...[more]

PMID: 22262763

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Project description:The frequency of delayed function of kidney transplants varies greatly and is associated with the quality of graft, donor age, and the duration of cold ischemia time. Body weight differences between donor and recipient can affect primary graft function. The underlying mechanism is poorly understood. Here, we have transplanted kidney grafts from commensurate body weight (L-WD) or reduced body weight (H-WD) donor rats into syngeneic or allogeneic recipients. 24 hours post-transplantation, serum creatinine level in H-WD recipients was significantly higher compared to that of L-WD recipients indicating impaired primary graft function. We detected a 10 fold higher transcription of IL-6 and dramatically increased tubular destruction in grafts from H-WD recipients. This was accompanied by decreased expression of genes associated with kidney function and an up-regulation of other genes such as cytochrome P450 isoforms, FosL and Trib3 as revealed by DNA microarray analysis. A single application of IL-6 into L-WD recipients is sufficient to impair primary graft function and to cause tubular damage. Whereas, immediate neutralization of IL-6 receptor signaling rescued primary graft function resulting in low serum creatinine levels, well-preserved kidney graft architecture and a normalized gene expression profile. These findings have strong clinical implication as anti-IL6R treatment of patients receiving grafts from lower-weight donors could be used to improve primary graft function. The dataset comprises eight samples divided into four sample groups. Each group represents rat kidneys collected after allogeneic transplantation under a certain condition and includes two biological replicates. The first group is characterized by a high body weight difference between donor and recipient, rats in the second group exhibit a low weight difference. Group three and four are similar to group one, but underwent an additional treatment with anti-IL6R mAb or prednisolone immediately after transplantation.

Project description:Objective: Apolipoprotein E (Apo E) is a multifunctional protein, originally described in the context of lipoprotein metabolism and cardiovascular disease. More recently, anti-inflammatory functions of ApoE have been documented. ApoE was studied in the context of several inflammatory disorders, but its role in the pathogenesis of acute organ rejection is unknown. In this study, we test the hypothesis that ApoE attenuates acute renal allograft rejection. Materials and methods: The Dark Agouti (DA) to Lewis (Lew) and the Brown Norway (BN) to Lew rat strain combinations were used to investigate fatal acute rejection. In addition, Fischer 344 (F344) kidneys were transplanted to Lew rats to study reversible acute rejection. Isograft recipients and untreated Lew rats were used as controls. ApoE mRNA expression was quantified in intravascular leukocytes accumulating in the blood vessels of renal grafts and in graft tissue. Apo E protein levels were assessed in blood plasma. To test the protective potential of ApoE, recipients of BN kidneys were treated with ApoE-mimetic peptide. Results: Intravascular graft leukocytes and renal tissue obtained from animals undergoing reversible acute rejection expressed increased levels of ApoE mRNA, whereas during fatal rejection, ApoE expression remained unchanged in the BN to Lew rat strain combination or was significantly reduced when DA rats were used as donors of the kidney. On the protein level, no changes in ApoE were seen in plasma. However, we do not know if local leukocytic ApoE expression results in increased ApoE concentrations inside graft blood vessels. Peptide treatment of allograft recipients reversed fatal rejection and significantly improved animal survival. Conclusions: ApoE plays a protective role in acute organ rejection. Further studies are needed to understand the exact mechanism how ApoE reverses acute rejection. dual-color balanced dye-swap design with 4 biological replicates, hybridized on 4 arrays

Dataset Information

Comparison between syngeneic kidney transplant and a model of allogeneic kidney transplant tolerance induced by anti-classII regimen in the rat

Publications

Transplant tolerance is associated with reduced expression of cystathionine-γ-lyase that controls IL-12 production by dendritic cells and TH-1 immune responses.

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