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Blood, 15 February 2008, Vol. 111, No. 4, pp. 2083-2090. Prepublished online as a Blood First Edition Paper on November 26, 2007; DOI 10.1182/blood-2007-08-108563. This Article Full Text Full Text (PDF) Supplemental Methods and Figure All Versions of this Article: blood-2007-08-108563v1 111/4/2083    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Jensen, C. T. Articles by Jacobsen, S. E. W. Search for Related Content PubMed PubMed Citation Articles by Jensen, C. T. Articles by Jacobsen, S. E. W. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Permissive roles of hematopoietin and cytokine tyrosine kinase receptors in early T-cell development Christina T. Jensen1,2, Charlotta Böiers1, Shabnam Kharazi1, Anna Lübking1, Tobias Rydén3, Mikael Sigvardsson1, Ewa Sitnicka1, and Sten Eirik W. Jacobsen1,2 1 Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, Lund, Sweden; 2 Haematopoietic Stem Cell Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom; and 3 Centre for Mathematical Sciences, Lund University, Lund, Sweden Although several cytokines have been demonstrated to be critical regulators of development of multiple blood cell lineages, it remains disputed to what degree they act through instructive or permissive mechanisms. Signaling through the FMS-like tyrosine kinase 3 (FLT3) receptor and the hematopoietin IL-7 receptor (IL-7R) has been demonstrated to be of critical importance for sustained thymopoiesis. Signaling triggered by IL-7 and thymic stromal lymphopoietin (TSLP) is dependent on IL-7R, and both ligands have been implicated in T-cell development. However, we demonstrate that, whereas thymopoiesis is abolished in adult mice doubly deficient in IL-7 and FLT3 ligand (FLT3L), TSLP does not play a key role in IL-7–independent or FLT3L-independent T lymphopoiesis. Furthermore, whereas previous studies implicated that the role of other cytokine tyrosine kinase receptors in T lymphopoiesis might not involve permissive actions, we demonstrate that ectopic expression of BCL2 is sufficient not only to partially correct the T-cell phenotype of Flt3l–/– mice but also to rescue the virtually complete loss of all discernable stages of early T lymphopoiesis in Flt3l–/–Il7r–/– mice. These findings implicate a permissive role of cytokine receptors of the hematopoietin and tyrosine kinase families in early T lymphopoiesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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