Permissive roles of hematopoietin and cytokine tyrosine kinase receptors in early T cell development

Research output: Contribution to journalArticle

Abstract

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 alpha (IL-7Ralpha) 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-7Ralpha, 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.

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Subject classification (UKÄ) – MANDATORY

  • Hematology
Original languageEnglish
Pages (from-to)2083-2090
JournalBlood
Volume111
Issue number4
Publication statusPublished - 2008
Publication categoryResearch
Peer-reviewedYes

Related research output

Kharazi, S., 2010, Lund Stem Cell Center, Faculty of Medicine, LU. 140 p.

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