Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Peripheral tissue instruction is the primary determinant of CD8+ T cell pathogenicity: transcription profiling by RNA-seq of CD8+ effector T cells isolated from the blood and skin of HSCT patients developing acute pattern GVHD.

ABSTRACT: To determine whether murine GVHD associated tissue-specific signatures of donor CD8+ effector T cells are conserved at the same locations in humans developing GVHD, we compared the transcriptional profile of CD8+ T cells obtained simultaneously from the blood and skin of 5 patients developing acute pattern skin GVHD.

INSTRUMENT(S): NextSeq 500

ORGANISM(S): Homo sapiens

SUBMITTER: Pedro Miguel Santos e Sousa

PROVIDER: E-MTAB-5381 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Peripheral tissues reprogram CD8+ T cells for pathogenicity during graft-versus-host disease.

Santos E Sousa Pedro P Ciré Séverine S Conlan Thomas T Jardine Laura L Tkacz Claire C Ferrer Ivana R IR Lomas Cara C Ward Sophie S West Heather H Dertschnig Simone S Blobner Sven S Means Terry K TK Henderson Stephen S Kaplan Daniel H DH Collin Matthew M Plagnol Vincent V Bennett Clare L CL Chakraverty Ronjon R

JCI insight 20180308 5

Graft-versus-host disease (GVHD) is a life-threatening complication of allogeneic stem cell transplantation induced by the influx of donor-derived effector T cells (TE) into peripheral tissues. Current treatment strategies rely on targeting systemic T cells; however, the precise location and nature of instructions that program TE to become pathogenic and trigger injury are unknown. We therefore used weighted gene coexpression network analysis to construct an unbiased spatial map of TE differenti ...[more]

PMID: 29515032

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Project description:Expression profiling of rat major histocompatibility complex and natural killer complex genes in skin explant assays reveals genes that are regulated in graft versus host disease. The major histocompatibility complex (MHC) is the most important genomic region that contributes to the genetic risk of graft rejection and graft versus host disease (GVHD) after haematopoietic stem cell transplantation. Therefore, MHC matching is most essential for the success of clinical transplantations. However, the MHC contains in addition to MHC class I and class II genes that are genotyped for selection of donors further so far unidentified genes that also contribute significantly to the risk to develop acute GVHD. It is difficult to identify these MHC genes by genetic association studies alone due to linkage disequilibrium in this region. Therefore, we aimed to identify MHC genes that might be involved in the pathohysiology of GVHD by expression profiling. To reduce the complexity of our model, we used genetically well-defined inbred rat strains (PVG and BN) and skin explant assays, an in-vitro-model of graft versus host reaction (GVHR), to analyse the expression of MHC and natural killer complex (NKC) genes in a cutaneous GVHR by a custom microarray. A higher percentage of genes in these immunologically highly important genomic regions were regulated than in the rest of the genome. We observed a statistically significant regulation of 25 MHC and 6 NKC genes and 168 other genes (i.e., 4.9%, 14.0%, and 6.6%, respectively) in rat skin explants cultured in the presence of pre-stimulated allogeneic lymphocytes compared to control samples cultured in the presence of syngeneic lymphocytes. Seven MHC and 3 NKC genes were selected for analysis by quantitative real-time polymerase chain reaction PCR. Most of the results of the microarray were confirmed in the same experimental set that was used for the microarray analysis and in a second independent experimental set of skin explant samples. In addition, GVHD-affected skin lesions of transplanted rats were analysed and similar regulations of most of the selected MHC and NKC genes were observed. Thus, our skin explant model of GVHR is informative for the gene regulation during GVHD. Interestingly, the human homologues of several of the regulated genes are polymorphic and could therefore contribute to the genetic risk of GVHD. These genes include RT1-Dmb, C2, Aif1, Spr1, Ubd, and Olr1. The human homologues of these genes might be useful for risk assessment and diagnosis of GVHD in patients. Two-condition experiment, Stimulated vs. NonSimulated cells. 12 Biological replicates, 2 Technical Replicates (Dye Swap) per Biological Replicate.

Dataset Information

Peripheral tissue instruction is the primary determinant of CD8+ T cell pathogenicity: transcription profiling by RNA-seq of CD8+ effector T cells isolated from the blood and skin of HSCT patients developing acute pattern GVHD.

Publications

Peripheral tissues reprogram CD8+ T cells for pathogenicity during graft-versus-host disease.

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