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Critical role of FLT3 ligand in IL-7 receptor-independent T lymphopoiesis and regulation of lymphoid-primed multipotent progenitors

Sitnicka Quinn, Ewa LU ; Buza-Vidas, Natalija LU ; Ahlenius, Henrik LU ; Cilio, Corrado LU ; Gekas, Christos LU ; Nygren, Jens LU ; Månsson, Robert LU ; Cheng, Min LU ; Jensen, Christina LU and Svensson Frej, Marcus LU , et al. (2007) In Blood 110(8). p.2955-2964
Abstract
The molecular pathways regulating lymphoid priming, fate, and development of multipotent bone marrow (BM) stem/ progenitor cells that continuously replace thymic progenitors remain largely unknown. Herein, we show that fms-like tyrosine kinase 3 (Flt3) figand (FI)-deficient mice have distinct reductions in the earliest thymic progenitors in fetal, postnatal, and adult thymus. A critical role of FL in thymopoiesis was particularly evident in the absence of interleukin-7 receptor alpha (IL-7R alpha) signaling. FI-/-II-7r(-/-) mice have extensive reductions in fetal and postnatal thymic progenitors that result in a loss of active thymopoiesis in adult mice, demonstrating an indispensable role of FL in IL-7R alpha independent fetal and adult T... (More)
The molecular pathways regulating lymphoid priming, fate, and development of multipotent bone marrow (BM) stem/ progenitor cells that continuously replace thymic progenitors remain largely unknown. Herein, we show that fms-like tyrosine kinase 3 (Flt3) figand (FI)-deficient mice have distinct reductions in the earliest thymic progenitors in fetal, postnatal, and adult thymus. A critical role of FL in thymopoiesis was particularly evident in the absence of interleukin-7 receptor alpha (IL-7R alpha) signaling. FI-/-II-7r(-/-) mice have extensive reductions in fetal and postnatal thymic progenitors that result in a loss of active thymopoiesis in adult mice, demonstrating an indispensable role of FL in IL-7R alpha independent fetal and adult T lymphopoiesis. Moreover, we establish a unique and critical role of FL, distinct from that of IL-7R alpha, in regulation of the earliest lineage-negative (Lin(-)) Lin(-)SCA1(+)KIT(+) (LSK) FLT3(hi) lymphoid primed multipotent progenitors in BM, demonstrating a key role of FLT3 signaling in regulating the very earliest stages of lymphoid progenitors. (Less)
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publishing date
type
Contribution to journal
publication status
published
subject
in
Blood
volume
110
issue
8
pages
2955 - 2964
publisher
American Society of Hematology
external identifiers
  • wos:000250426700034
  • scopus:35548939080
ISSN
1528-0020
DOI
10.1182/blood-2006-10-054726
language
English
LU publication?
yes
id
4e0bdea9-83e0-42c4-8b37-c3aa9a1e79ef (old id 653223)
date added to LUP
2007-12-19 14:51:00
date last changed
2017-11-12 03:27:30
@article{4e0bdea9-83e0-42c4-8b37-c3aa9a1e79ef,
  abstract     = {The molecular pathways regulating lymphoid priming, fate, and development of multipotent bone marrow (BM) stem/ progenitor cells that continuously replace thymic progenitors remain largely unknown. Herein, we show that fms-like tyrosine kinase 3 (Flt3) figand (FI)-deficient mice have distinct reductions in the earliest thymic progenitors in fetal, postnatal, and adult thymus. A critical role of FL in thymopoiesis was particularly evident in the absence of interleukin-7 receptor alpha (IL-7R alpha) signaling. FI-/-II-7r(-/-) mice have extensive reductions in fetal and postnatal thymic progenitors that result in a loss of active thymopoiesis in adult mice, demonstrating an indispensable role of FL in IL-7R alpha independent fetal and adult T lymphopoiesis. Moreover, we establish a unique and critical role of FL, distinct from that of IL-7R alpha, in regulation of the earliest lineage-negative (Lin(-)) Lin(-)SCA1(+)KIT(+) (LSK) FLT3(hi) lymphoid primed multipotent progenitors in BM, demonstrating a key role of FLT3 signaling in regulating the very earliest stages of lymphoid progenitors.},
  author       = {Sitnicka Quinn, Ewa and Buza-Vidas, Natalija and Ahlenius, Henrik and Cilio, Corrado and Gekas, Christos and Nygren, Jens and Månsson, Robert and Cheng, Min and Jensen, Christina and Svensson Frej, Marcus and Leandersson, Karin and Agace, William and Sigvardsson, Mikael and Jacobsen, Sten Eirik W},
  issn         = {1528-0020},
  language     = {eng},
  number       = {8},
  pages        = {2955--2964},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Critical role of FLT3 ligand in IL-7 receptor-independent T lymphopoiesis and regulation of lymphoid-primed multipotent progenitors},
  url          = {http://dx.doi.org/10.1182/blood-2006-10-054726},
  volume       = {110},
  year         = {2007},
}