Permissive roles of hematopoietin and cytokine tyrosine kinase receptors in early T cell development
Dokumenttyp: Artikel i tidskrift
Förlag: American Society of Hematology
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.
- ISSN: 1528-0020