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Roles of hematopoietin and cytokine tyrosine kinase receptors in early lymphopoiesis

Jensen, Christina LU (2007) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2007:171.
Abstract
Cytokines have been shown to have important roles in lymphopoiesis. However, many questions remain unresolved. Among other, while the action of interleukin (IL)-7 in alpha beta T cell development in mouse seems to be largely mediated through permissive survival signaling, the possible permissive role of IL-7 in early B cell development is disputed. Furthermore, FMS-like tyrosine kinase-3 ligand (FLT3L) has been shown to be important in IL-7 receptor alpha chain (IL-7R)-independent B and T lymphopoiesis but little is known of its mode(s) of action. Moreover, although little direct evidence exists, thymic stromal lymphopoietin (TSLP) has been suggested to be a key regulator of fetal and adult IL-7-independent lymphopoiesis. Herein, I... (More)
Cytokines have been shown to have important roles in lymphopoiesis. However, many questions remain unresolved. Among other, while the action of interleukin (IL)-7 in alpha beta T cell development in mouse seems to be largely mediated through permissive survival signaling, the possible permissive role of IL-7 in early B cell development is disputed. Furthermore, FMS-like tyrosine kinase-3 ligand (FLT3L) has been shown to be important in IL-7 receptor alpha chain (IL-7R)-independent B and T lymphopoiesis but little is known of its mode(s) of action. Moreover, although little direct evidence exists, thymic stromal lymphopoietin (TSLP) has been suggested to be a key regulator of fetal and adult IL-7-independent lymphopoiesis. Herein, I explored, through studies of single and double cytokine receptor and ligand knockout mice, the relative roles of TSLP, IL-7 and FLT3L as well as a potential permissive role for FLT3L and IL-7 in early B and T cell development.

We demonstrate that rather than TSLP, IL-7 and FLT3L are critical for B and T cell generation in mice. Furthermore, we demonstrate that ectopic expression of B cell lymphoma 2 (BCL2) is sufficient not only to correct the T cell phenotype of FLT3L deficient mice but can also rescue the virtually complete loss of all discernable stages of early T lymphopoiesis in double FLT3L and IL-7R deficient mice. Furthermore, the same overexpression studies suggest that FLT3 and IL-7R are capable of also mediating survival signaling in early B cell development. These findings implicate a permissive role of cytokine receptors of the hematopoietin as well as the tyrosine kinase families in early B and T lymphopoiesis. (Less)
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author
supervisor
opponent
  • Ph.D Allman, David, University of Pennsylvania School of Medicine
organization
publishing date
type
Thesis
publication status
published
subject
keywords
IL -7, FLT3 Ligand, cytokines, lymphopoiesis, hematopoiesis, TSLP, apoptosis
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2007:171
pages
159 pages
publisher
Hematopoietic Stem Cell Laboratory
defense location
BMC Segerfalksalen
defense date
2007-12-20 09:00
ISSN
1652-8220
ISBN
978-91-85897-49-0
language
English
LU publication?
yes
id
ce30f7d6-6676-4c89-beec-77ffe92d1953 (old id 633906)
date added to LUP
2007-12-19 16:37:00
date last changed
2016-09-19 08:44:57
@phdthesis{ce30f7d6-6676-4c89-beec-77ffe92d1953,
  abstract     = {Cytokines have been shown to have important roles in lymphopoiesis. However, many questions remain unresolved. Among other, while the action of interleukin (IL)-7 in alpha beta T cell development in mouse seems to be largely mediated through permissive survival signaling, the possible permissive role of IL-7 in early B cell development is disputed. Furthermore, FMS-like tyrosine kinase-3 ligand (FLT3L) has been shown to be important in IL-7 receptor alpha chain (IL-7R)-independent B and T lymphopoiesis but little is known of its mode(s) of action. Moreover, although little direct evidence exists, thymic stromal lymphopoietin (TSLP) has been suggested to be a key regulator of fetal and adult IL-7-independent lymphopoiesis. Herein, I explored, through studies of single and double cytokine receptor and ligand knockout mice, the relative roles of TSLP, IL-7 and FLT3L as well as a potential permissive role for FLT3L and IL-7 in early B and T cell development.<br/><br>
We demonstrate that rather than TSLP, IL-7 and FLT3L are critical for B and T cell generation in mice. Furthermore, we demonstrate that ectopic expression of B cell lymphoma 2 (BCL2) is sufficient not only to correct the T cell phenotype of FLT3L deficient mice but can also rescue the virtually complete loss of all discernable stages of early T lymphopoiesis in double FLT3L and IL-7R deficient mice. Furthermore, the same overexpression studies suggest that FLT3 and IL-7R are capable of also mediating survival signaling in early B cell development. These findings implicate a permissive role of cytokine receptors of the hematopoietin as well as the tyrosine kinase families in early B and T lymphopoiesis.},
  author       = {Jensen, Christina},
  isbn         = {978-91-85897-49-0},
  issn         = {1652-8220},
  keyword      = {IL -7,FLT3 Ligand,cytokines,lymphopoiesis,hematopoiesis,TSLP,apoptosis},
  language     = {eng},
  pages        = {159},
  publisher    = {Hematopoietic Stem Cell Laboratory},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {Roles of hematopoietin and cytokine tyrosine kinase receptors in early lymphopoiesis},
  volume       = {2007:171},
  year         = {2007},
}