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Distinct and overlapping patterns of cytokine regulation of thymic and bone marrow-derived NK cell development.

Cheng, Min LU ; Charoudeh, Hojjatollah Nozad; Brodin, Petter; Tang, Yanjuan; Lakshmikanth, Tadepally; Höglund, Petter; Jacobsen, Sten Eirik W LU and Sitnicka Quinn, Ewa LU (2009) In Journal of immunology (Baltimore, Md. : 1950) 182(3). p.1460-1468
Abstract
Although bone marrow (BM) represents the main site for postnatal NK cell development, recently a distinct thymic-dependent NK cell pathway was identified. These studies were designed to investigate the role of cytokines in regulation of thymic NK cells and to compare with established regulatory pathways of BM-dependent NK cell compartment. The common cytokine receptor gamma-chain (Il2rg) essential for IL-15-induced signaling, and FMS-like tyrosine kinase 3 (FLT3) receptor ligand (Flt3l) were previously identified as important regulatory pathways of the BM NK cell compartment based on lack of function studies in mice, however their complementary action remains unknown. By investigating mice double-deficient in Il2rg and Flt3l (Flt3l(-/-)... (More)
Although bone marrow (BM) represents the main site for postnatal NK cell development, recently a distinct thymic-dependent NK cell pathway was identified. These studies were designed to investigate the role of cytokines in regulation of thymic NK cells and to compare with established regulatory pathways of BM-dependent NK cell compartment. The common cytokine receptor gamma-chain (Il2rg) essential for IL-15-induced signaling, and FMS-like tyrosine kinase 3 (FLT3) receptor ligand (Flt3l) were previously identified as important regulatory pathways of the BM NK cell compartment based on lack of function studies in mice, however their complementary action remains unknown. By investigating mice double-deficient in Il2rg and Flt3l (Flt3l(-/-) Il2rg(-/-)), we demonstrate that FLT3L is important for IL2Rg-independent maintenance of both immature BM as well as peripheral NK cells. In contrast to IL-7, which is dispensable for BM but important for thymic NK cells, IL-15 has a direct and important role in both thymic and BM NK cell compartments. Although thymic NK cells were not affected in Flt3l(-/-) mice, Flt3l(-/-)Il2rg(-/-) mice lacked detectable thymic NK cells, suggesting that FLT3L is also important for IL-2Rg-independent maintenance of thymic NK cells. Thus, IL-2Rg cytokines and FLT3L play complementary roles and are indispensable for homeostasis of both BM and thymic dependent NK cell development, suggesting that the cytokine pathways crucial for these two distinct NK cell pathways are largely overlapping. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of immunology (Baltimore, Md. : 1950)
volume
182
issue
3
pages
1460 - 1468
publisher
American Association of Immunologists
external identifiers
  • WOS:000262842100030
  • PMID:19155493
  • Scopus:63149188715
ISSN
1550-6606
language
English
LU publication?
yes
id
56b1ed1a-1c21-494d-92d1-9cfbadf6785d (old id 1289490)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19155493?dopt=Abstract
date added to LUP
2009-02-04 13:05:02
date last changed
2016-11-01 10:16:41
@misc{56b1ed1a-1c21-494d-92d1-9cfbadf6785d,
  abstract     = {Although bone marrow (BM) represents the main site for postnatal NK cell development, recently a distinct thymic-dependent NK cell pathway was identified. These studies were designed to investigate the role of cytokines in regulation of thymic NK cells and to compare with established regulatory pathways of BM-dependent NK cell compartment. The common cytokine receptor gamma-chain (Il2rg) essential for IL-15-induced signaling, and FMS-like tyrosine kinase 3 (FLT3) receptor ligand (Flt3l) were previously identified as important regulatory pathways of the BM NK cell compartment based on lack of function studies in mice, however their complementary action remains unknown. By investigating mice double-deficient in Il2rg and Flt3l (Flt3l(-/-) Il2rg(-/-)), we demonstrate that FLT3L is important for IL2Rg-independent maintenance of both immature BM as well as peripheral NK cells. In contrast to IL-7, which is dispensable for BM but important for thymic NK cells, IL-15 has a direct and important role in both thymic and BM NK cell compartments. Although thymic NK cells were not affected in Flt3l(-/-) mice, Flt3l(-/-)Il2rg(-/-) mice lacked detectable thymic NK cells, suggesting that FLT3L is also important for IL-2Rg-independent maintenance of thymic NK cells. Thus, IL-2Rg cytokines and FLT3L play complementary roles and are indispensable for homeostasis of both BM and thymic dependent NK cell development, suggesting that the cytokine pathways crucial for these two distinct NK cell pathways are largely overlapping.},
  author       = {Cheng, Min and Charoudeh, Hojjatollah Nozad and Brodin, Petter and Tang, Yanjuan and Lakshmikanth, Tadepally and Höglund, Petter and Jacobsen, Sten Eirik W and Sitnicka Quinn, Ewa},
  issn         = {1550-6606},
  language     = {eng},
  number       = {3},
  pages        = {1460--1468},
  publisher    = {ARRAY(0xaf4b628)},
  series       = {Journal of immunology (Baltimore, Md. : 1950)},
  title        = {Distinct and overlapping patterns of cytokine regulation of thymic and bone marrow-derived NK cell development.},
  volume       = {182},
  year         = {2009},
}