Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Role of AhR in thymocyte emigration in vivo

ABSTRACT: Over-activation of the aryl hydrocarbon receptor by TCDD in mice leads among other phenotypes to a severe thymic atrophy accompanied by immunosuppression. TCDD causes a block in thymocyte maturation and a preferential emigration of immature CD4-CD8- DN thymocytes (recent thymic emigrants) into the periphery. As part of this study gene expression profiles from DN thymocytes and thymic emigrants were generated from TCDD and solvent control mice Keywords: Affymetrix, TCDD, CD4-CD8- thymocytes, Thymus involution, thymic emigration, Ahr Female, 6-8 week old C57BL6 mice were i.p. injected with 10 M-BM-5g/kg TCDD. After 5 days mice were anesthezised and FITC injected into their thymi. after 24h mice were sacrificed and CD4-CD8-FITC+ cells isolated from thymus (thymocytes) and spleen (recent thymus emigrants).

ORGANISM(S): Mus musculus

SUBMITTER: Markus Frericks

PROVIDER: E-GEOD-10166 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Role of the aryl hydrocarbon receptor in thymocyte emigration in vivo.

Temchura Vladimir V VV Frericks Markus M Nacken Wolfgang W Esser Charlotte C

European journal of immunology 20050901 9

The aryl hydrocarbon receptor (AHR) is a ligand-dependent member of the PAS-bHLH-family of nuclear receptors. Anthropogenic ligands include environmental contaminants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Over-activation of the AHR causes thymus atrophy and immunosuppression. Signaling via the AHR changes the thymocyte differentiation program at several checkpoints, in particular within the CD4-CD8- double-negative (DN) thymocyte subset. Here, we show that AHR over-activation led t ...[more]

PMID: 16114106

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Project description:The thymus constitutes the primary lymphoid organ for the majority of T cells. The phosphatidyl-inositol 3 kinase (PI3K) signaling pathway is involved in lymphoid development. Defects in single components of this pathway prevent thymocytes from progressing beyond early T cell developmental stages. Protein kinase B (PKB) is the main effector of the PI3K pathway. To determine whether PKB mediates PI3K signaling in early T cell development, we characterized PKB knockout thymi. Our results reveal a significant thymic hypocellularity in PKBalpha-/- neonates and an accumulation of early thymocyte subsets in PKBalpha-/- adult mice. The latter finding is specifically attributed to the lack of PKBalpha within the lymphoid component of the thymus. Microarray analyses show that the absence of PKBalpha in early thymocyte subsets modifies the expression of genes known to be involved in pre-TCR signaling, in T cell activation, and in the transduction of interferon-mediated signals. This report highlights the specific requirements of PKBalpha for thymic development. Experiment Overall Design: Early thymocyte subsets (DN3 and ISP8) were sorted by FACS from 4 PKBalpha-/- / PKBalpha+/+ mouse littermate pairs. The same number of DN3 or ISP8 cells was sorted (7 000 to 25 000 cells) within a PKBalpha-/- / PKBalpha+/+ pair. Four replicates per condition were then analysed (4xPKBalpha-/- DN3, 4xPKBalpha+/+ DN3, 4xPKBalpha-/- ISP8, 4xPKBalpha+/+ ISP8). Total RNA was extracted using PicoPureTM RNA isolation kit (Arcturus, Sunnyvale, CA, USA) and RNA quality was controlled using the 2100 Bioanalyser (Agilent Technologies, Santa Clara, CA, USA). Total RNA was amplified and labeled using the Affymetrix 2-cycle 3â labelling kit according to manufacturerâs instructions. After fragmentation, 10 ug cRNA was hybridised to mouse genome 430 2.0 GeneChips (Affymetrix, Santa Clara, CA). The supplementary file represents the expression values estimated using the GC-RMA function provided by Refiner 3.1 (Genedata, Basel, Switzerland) for each of the samples.

Dataset Information

Role of AhR in thymocyte emigration in vivo

Publications

Role of the aryl hydrocarbon receptor in thymocyte emigration in vivo.

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