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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 (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 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 HighWire 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 22, 2007 Accepted November 3, 2007 Permissive roles of hematopoietin and cytokine tyrosine kinase receptors in early T cell development Christina T Jensen, Charlotta Boiers, Shabnam Kharazi, Anna Lubking, Tobias Ryden, Mikael Sigvardsson, Ewa Sitnicka, and Sten Eirik W. Jacobsen* Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, Lund, Sweden Mathematical Statistics, Centre for Mathematical Sciences, Lund, Sweden Hematopoietic Stem Cell Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom * Corresponding author; email: sten.jacobsen{at}med.lu.se. Although a number of 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) have been demonstrated to be of critical importance for sustained thymopoiesis. Signaling triggered by IL-7 and thymic stromal lymphopoietin (TSLP) are dependent on IL-7R, and both ligands have been implicated in T cell development. However we demonstrate here that while thymopoiesis is completely abolished in 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 suggested that the role of cytokine tyrosine kinase receptors in T lymphopoiesis might not involve permissive actions, we demonstrate that ectopic expression of BCL2 is sufficient not only to correct the T cell phenotype of Flt3l-/- mice but significantly, can also rescue the virtually complete loss of all discernable stages of early T lymphopoiesis in Flt3l-/-Il7r-/- mice. These findings implicate a critical permissive role of cytokine receptors of the hematopoietin as well as the tyrosine kinase families in early T lymphopoiesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Cheng, H. N. Charoudeh, P. Brodin, Y. Tang, T. Lakshmikanth, P. Hoglund, S. E. W. Jacobsen, and E. Sitnicka Distinct and Overlapping Patterns of Cytokine Regulation of Thymic and Bone Marrow-Derived NK Cell Development J. Immunol., February 1, 2009; 182(3): 1460 - 1468. [Abstract] [Full Text] [PDF]

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