A General Survey of Thymocyte Differentiation by Transcriptional Analysis of Knockout Mouse Models

Puthier, Denis; Joly, Florence; Irla, Magali; Saade, Murielle; Victoréro, Geneviève; Loriod, Béatrice; Nguyen, Catherine

doi:10.4049/jimmunol.173.10.6109

Cited by 27 publications

(38 citation statements)

References 65 publications

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“…Ϫ cells have a lower threshold for ligand-independent pre-TCR signaling, based in part on increased Ca 2ϩ capacitive entry (20,45). This is significant, considering that such Ca 2ϩ flux-mediated signaling normally represses full-length p51-Ets1, but not p42-Ets1, transcriptional activity.…”

Section: Cd8mentioning

confidence: 96%

Thymomegaly, Microsplenia, and Defective Homeostatic Proliferation of Peripheral Lymphocytes in p51-Ets1 Isoform-Specific Null Mice

Higuchi

Bartel

Masuya³

et al. 2007

Molecular and Cellular Biology

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Ets1 is a member of the Ets transcription factor family. Alternative splicing of exon VII results in two naturally occurring protein isoforms: full-length Ets1 (p51-Ets1) and Ets1⌬VII (p42-Ets1). These isoforms bear key distinctions regarding protein-protein interactions, DNA binding kinetics, and transcriptional target specificity. Disruption of both Ets1 isoforms in mice results in the loss of detectable NK and NKT cell activity and defects in B and T lymphocytes. We generated mice that express only the Ets1 ⌬VII isoform. Ets1⌬VII homozygous mice express no p51-Ets1 and elevated levels of the p42-Ets1 protein relative to the wild type and display increased perinatal lethality, thymomegaly, and peripheral lymphopenia. Proliferation was increased in both the thymus and the spleen, while apoptosis was decreased in the thymus and increased in the spleen of homozygotes. Significant elevations of CD8 ؉ and CD8 ؉ CD4 ؉ thymocytes were observed. Lymphoid cell (CD19 ؉ , CD4 ؉ , and CD8 ؉ ) reductions were predominantly responsible for diminished spleen cellularity, with fewer memory cells and a failure of homeostatic proliferation to maintain peripheral lymphocytes. Collectively, the Ets1⌬VII mutants demonstrate lymphocyte maturation defects associated with misregulation of p16 Ink4a , p27Kip1 , and CD44. Thus, a balance in the differential regulation of Ets1 isoforms represents a potential mechanism in the control of lymphoid maturation and homeostasis.

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Section: Cd8mentioning

confidence: 96%

Thymomegaly, Microsplenia, and Defective Homeostatic Proliferation of Peripheral Lymphocytes in p51-Ets1 Isoform-Specific Null Mice

Higuchi

Bartel

Masuya³

et al. 2007

Molecular and Cellular Biology

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“…on April 27, 2019. by guest www.bloodjournal.org From and subtracted as described. 27 For each sample, the 6000 highest values were flagged.…”

Section: Data Processing and Analysismentioning

confidence: 99%

“…For each array, background intensity was calculated on the basis of the average of the 400 lowest values and subtracted as described. 27 For each sample, the 6000 highest values were flagged.…”

Section: Data Processing and Analysismentioning

confidence: 99%

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Thrombin-induced endothelial microparticle generation: identification of a novel pathway involving ROCK-II activation by caspase-2

Sapet

Simoncini

Loriod

et al. 2006

Blood

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192

151

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Thrombin exerts pleiotropic effects on endothelial cells, including the release of microparticles (EMPs) that disseminate and exchange information with vascular cells. Nevertheless, the mechanisms leading to their generation are not elucidated. We performed microarray analysis to identify genes involved in EMP release by the endothelial cell line HMEC-1 in response to thrombin. We identified a group of genes linked to the cytoskeleton reorganization family. Among these, the Rhokinase ROCK-II presented a high transcription rate. ROCK-I, another Rhokinase isoform, was not modulated by thrombin. Pharmacologic inhibition of Rho-kinases or specific depletion of ROCK-II by short interfering (si) RNA inhibited thrombin-induced EMP release. In contrast, ROCK-I mRNA silencing did not modify EMP generation by thrombin. Exposure of HMEC-1 to thrombin in presence of the caspase-2 selective inhibitor Z-VDVAD-FMK prevented ROCK-II cleavage and inhibited the thrombin-induced EMP release. These events were observed in absence of cell death. Our data clearly identified ROCK-II as a target of thrombin in EMP generation. They indicated that the 2 Rho-kinases did not share identical functions. The involvement of caspase-2 in ROCK-II activation independently of cell death points out a novel signaling pathway that emphasizes the proteolytic activity of caspase in EMP generation in response to cell activation. IntroductionThrombin is a serine protease playing a central role in the coagulation cascade and hemostasis. Generated at sites of vascular injury in the vicinity of a thrombus, thrombin promotes platelet activation, adhesion, and trafficking of inflammatory cells into sites of injury. 1 Moreover, thrombin exerts pleiotropic effects on the endothelium controlling the proliferative/reparative responses to injury and promoting both proinflammatory and procoagulant endothelial phenotypes. 2 Thrombin activities are mediated by the activation of the G-protein-linked protease-activated receptors (PARs), mainly PAR-1 on the endothelial cells. 3 Recently, the gene profiling of primary endothelial cells in response to thrombin indicates changes in the transcription of a multitude of genes, 2,4 which results in modifications of the endothelial cell shape, cytoskeleton rearrangement, and increased permeability. 5 Despite the large body of experiments describing the effects of thrombin on the endothelium, little is known on its capacity to generate endothelial cell microparticles 6 and the mechanisms involved in their release have never been reported.Microparticles found in the extracellular space derive from membrane blebs. Blebbing is a reversible dynamic event that occurs during cell activation or apoptosis. 7 Viable cells display plasma membrane blebbing when spreading, migrating, dividing, or under conditions of stress. Blebbing depends on intracellular forces generated by the actin-myosin cytoskeleton and is driven through the activation of actin-myosin contraction 8,9 by the small GTP-binding protein Rho and its major effectors, the ...

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“…The nylon microarrays used for this study were produced as described (29) using the same bacterial clones except that 289 of them were replaced by IMAGE clones (Deutsches Ressourcenzentrum für Genomforschung Resource Centre, Berlin, Germany) representing mostly cytokines, their receptors and CD8 T cell-expressed genes. The final clone set includes 8668 bacterial clones representing 7750 nonredundant Unigene clusters.…”

Section: Gene Expression Profilingmentioning

confidence: 99%

CD8 T Cell Help for Innate Antitumor Immunity

Shanker

Verdeil

Buferne

et al. 2007

The Journal of Immunology

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Innate immunity is considered to initiate adaptive antitumor responses. We demonstrate that monoclonal CD8 T lymphocytes reactive to tumor Ag P1A on P815 mastocytoma cells provide essential “help” to NK cells for rejection of P1A-deficient tumors. RAG-deficient mice have normal NK cells but do not reject either tumor. Reconstitution of these mice with P1A-specific T cells conferred resistance to both P1A-expressing and -deficient tumor cells provided they were present at the same site. Elimination of Ag-negative tumor variants required both activated T and NK cells. Gene expression profiling of NK cells infiltrating P1A-positive tumors in mice with specific CD8 T cells demonstrated an activated effector phenotype. However, CD8 T cell help to NK cells appeared ineffective for P1A-negative variants separated from the P1A-positive tumor. Local tumor Ag-specific T cell-NK cell collaboration results in the elimination of tumor cells whether they express or not the T cell tumor Ag epitope, thus containing the emergence of tumor escape variants before metastasis.

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A General Survey of Thymocyte Differentiation by Transcriptional Analysis of Knockout Mouse Models

Cited by 27 publications

References 65 publications

Thymomegaly, Microsplenia, and Defective Homeostatic Proliferation of Peripheral Lymphocytes in p51-Ets1 Isoform-Specific Null Mice

Thymomegaly, Microsplenia, and Defective Homeostatic Proliferation of Peripheral Lymphocytes in p51-Ets1 Isoform-Specific Null Mice

Thrombin-induced endothelial microparticle generation: identification of a novel pathway involving ROCK-II activation by caspase-2

CD8 T Cell Help for Innate Antitumor Immunity

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