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  1. Article ; Online: Responsiveness of Developing T Cells to IL-7 Signals Is Sustained by miR-17∼92.

    Regelin, Malte / Blume, Jonas / Pommerencke, Jens / Vakilzadeh, Ramin / Witzlau, Katrin / Łyszkiewicz, Marcin / Ziętara, Natalia / Saran, Namita / Schambach, Axel / Krueger, Andreas

    Journal of immunology (Baltimore, Md. : 1950)

    2015  Volume 195, Issue 10, Page(s) 4832–4840

    Abstract: miRNAs regulate a large variety of developmental processes including development of the immune system. T cell development is tightly controlled through the interplay of transcriptional programs and cytokine-mediated signals. However, the role of ... ...

    Abstract miRNAs regulate a large variety of developmental processes including development of the immune system. T cell development is tightly controlled through the interplay of transcriptional programs and cytokine-mediated signals. However, the role of individual miRNAs in this process remains largely elusive. In this study, we demonstrated that hematopoietic cell-specific loss of miR-17∼92, a cluster of six miRNAs implicated in B and T lineage leukemogenesis, resulted in profound defects in T cell development both at the level of prethymic T cell progenitors as well as intrathymically. We identified reduced surface expression of IL-7R and concomitant limited responsiveness to IL-7 signals as a common mechanism resulting in reduced cell survival of common lymphoid progenitors and thymocytes at the double-negative to double-positive transition. In conclusion, we identified miR-17∼92 as a critical modulator of multiple stages of T cell development.
    MeSH term(s) Animals ; Animals, Genetically Modified ; B-Lymphocytes/cytology ; B-Lymphocytes/immunology ; Cell Survival/genetics ; Cell Survival/immunology ; Interleukin-7/genetics ; Interleukin-7/immunology ; Mice ; MicroRNAs/genetics ; MicroRNAs/immunology ; Receptors, Interleukin-17/genetics ; Receptors, Interleukin-17/immunology ; Signal Transduction/physiology ; T-Lymphocytes/cytology ; T-Lymphocytes/immunology
    Chemical Substances Il17r protein, mouse ; Interleukin-7 ; MicroRNAs ; Mirn17 microRNA, mouse ; Receptors, Interleukin-17 ; interleukin-7, mouse
    Language English
    Publishing date 2015-11-15
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3056-9
    ISSN 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
    ISSN (online) 1550-6606
    ISSN 0022-1767 ; 1048-3233 ; 1047-7381
    DOI 10.4049/jimmunol.1402248
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Ud II Zs.37: Show issues Location:
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    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)
    Zs.MG 28: Show issues

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  2. Article ; Online: Multiple extrathymic precursors contribute to T-cell development with different kinetics.

    Saran, Namita / Łyszkiewicz, Marcin / Pommerencke, Jens / Witzlau, Katrin / Vakilzadeh, Ramin / Ballmaier, Matthias / von Boehmer, Harald / Krueger, Andreas

    Blood

    2009  Volume 115, Issue 6, Page(s) 1137–1144

    Abstract: T-cell development in the thymus depends on continuous supply of T-cell progenitors from bone marrow (BM). Several extrathymic candidate progenitors have been described that range from multipotent cells to lymphoid cell committed progenitors and even ... ...

    Abstract T-cell development in the thymus depends on continuous supply of T-cell progenitors from bone marrow (BM). Several extrathymic candidate progenitors have been described that range from multipotent cells to lymphoid cell committed progenitors and even largely T-lineage committed precursors. However, the nature of precursors seeding the thymus under physiologic conditions has remained largely elusive and it is not known whether there is only one physiologic T-cell precursor population or many. Here, we used a competitive in vivo assay based on depletion rather than enrichment of classes of BM-derived precursor populations, thereby only minimally altering physiologic precursor ratios to assess the contribution of various extrathymic precursors to T-lineage differentiation. We found that under these conditions multiple precursors, belonging to both multipotent progenitor (MPP) and common lymphoid progenitor (CLP) subsets have robust T-lineage potential. However, differentiation kinetics of different precursors varied considerably, which might ensure continuous thymic output despite gated importation of extrathymic precursors. In conclusion, our data suggest that the thymus functions to impose T-cell fate on any precursor capable of filling the limited number of progenitor niches.
    MeSH term(s) Animals ; Bone Marrow Cells/immunology ; Cell Differentiation ; Cell Lineage ; Flow Cytometry ; Hematopoiesis ; Lymphocyte Activation ; Lymphoid Progenitor Cells/immunology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Multipotent Stem Cells/immunology ; Precursor Cells, T-Lymphoid/cytology ; Precursor Cells, T-Lymphoid/immunology ; Receptors, Interleukin-7/physiology ; T-Lymphocytes/immunology ; Thymus Gland/immunology
    Chemical Substances Receptors, Interleukin-7
    Language English
    Publishing date 2009-12-15
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood-2009-07-230821
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Uh III Zs.140: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 364: Show issues

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