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

Jensen, Christina LU ; Böiers, Charlotta LU ; Kharazi, Shabnam LU ; Lübking, Anna LU ; Rydén, Tobias LU ; Sigvardsson, Mikael LU ; Sitnicka Quinn, Ewa LU and Jacobsen, Sten Eirik W LU (2008) In Blood 111(4). p.2083-2090
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood
volume
111
issue
4
pages
2083 - 2090
publisher
American Society of Hematology
external identifiers
  • pmid:18039955
  • wos:000253251100056
  • scopus:41349111284
ISSN
1528-0020
DOI
10.1182/blood-2007-08-108563
language
English
LU publication?
yes
id
49662514-d9a6-43f8-bd6e-ad4145223fa5 (old id 1141632)
date added to LUP
2008-08-12 12:57:06
date last changed
2017-07-30 03:51:16
@article{49662514-d9a6-43f8-bd6e-ad4145223fa5,
  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.},
  author       = {Jensen, Christina and Böiers, Charlotta and Kharazi, Shabnam and Lübking, Anna and Rydén, Tobias and Sigvardsson, Mikael and Sitnicka Quinn, Ewa and Jacobsen, Sten Eirik W},
  issn         = {1528-0020},
  language     = {eng},
  number       = {4},
  pages        = {2083--2090},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Permissive roles of hematopoietin and cytokine tyrosine kinase receptors in early T cell development},
  url          = {http://dx.doi.org/10.1182/blood-2007-08-108563},
  volume       = {111},
  year         = {2008},
}