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Loss of Canonical Notch Signaling Affects Multiple Steps in NK Cell Development in Mice

Chaves, Patricia LU ; Zriwil, Alya LU ; Wittmann, Lilian LU ; Boukarabila, Hanane; Peitzsch, Claudia; Jacobsen, Sten Eirik W. LU and Sitnicka, Ewa LU (2018) In Journal of immunology (Baltimore, Md. : 1950) 201(11). p.3307-3319
Abstract

Within the hematopoietic system, the Notch pathway is critical for promoting thymic T cell development and suppressing the B and myeloid lineage fates; however, its impact on NK lymphopoiesis is less understood. To study the role of Notch during NK cell development in vivo, we investigated different NK cell compartments and function in Rbp-Jkfl/flVav-Cretg/+ mice, in which Rbp-Jk, the major transcriptional effector of canonical Notch signaling, was specifically deleted in all hematopoietic cells. Peripheral conventional cytotoxic NK cells in Rbp-Jk-deleted mice were significantly reduced and had an activated phenotype. Furthermore, the pool of early NK cell progenitors in the bone marrow was decreased, whereas immature NK cells were... (More)

Within the hematopoietic system, the Notch pathway is critical for promoting thymic T cell development and suppressing the B and myeloid lineage fates; however, its impact on NK lymphopoiesis is less understood. To study the role of Notch during NK cell development in vivo, we investigated different NK cell compartments and function in Rbp-Jkfl/flVav-Cretg/+ mice, in which Rbp-Jk, the major transcriptional effector of canonical Notch signaling, was specifically deleted in all hematopoietic cells. Peripheral conventional cytotoxic NK cells in Rbp-Jk-deleted mice were significantly reduced and had an activated phenotype. Furthermore, the pool of early NK cell progenitors in the bone marrow was decreased, whereas immature NK cells were increased, leading to a block in NK cell maturation. These changes were cell intrinsic as the hematopoietic chimeras generated after transplantation of Rbp-Jk-deficient bone marrow cells had the same NK cell phenotype as the Rbp-Jk-deleted donor mice, whereas the wild-type competitors did not. The expression of several crucial NK cell regulatory pathways was significantly altered after Rbp-Jk deletion. Together, these results demonstrate the involvement of canonical Notch signaling in regulation of multiple stages of NK cell development.

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author
organization
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type
Contribution to journal
publication status
published
subject
in
Journal of immunology (Baltimore, Md. : 1950)
volume
201
issue
11
pages
13 pages
publisher
American Association of Immunologists
external identifiers
  • scopus:85056719451
ISSN
1550-6606
DOI
10.4049/jimmunol.1701675
language
English
LU publication?
yes
id
b01dcc0a-0ba4-4b37-bccf-640e2a4a3db3
date added to LUP
2018-11-26 15:12:14
date last changed
2019-02-20 11:37:50
@article{b01dcc0a-0ba4-4b37-bccf-640e2a4a3db3,
  abstract     = {<p>Within the hematopoietic system, the Notch pathway is critical for promoting thymic T cell development and suppressing the B and myeloid lineage fates; however, its impact on NK lymphopoiesis is less understood. To study the role of Notch during NK cell development in vivo, we investigated different NK cell compartments and function in Rbp-Jkfl/flVav-Cretg/+ mice, in which Rbp-Jk, the major transcriptional effector of canonical Notch signaling, was specifically deleted in all hematopoietic cells. Peripheral conventional cytotoxic NK cells in Rbp-Jk-deleted mice were significantly reduced and had an activated phenotype. Furthermore, the pool of early NK cell progenitors in the bone marrow was decreased, whereas immature NK cells were increased, leading to a block in NK cell maturation. These changes were cell intrinsic as the hematopoietic chimeras generated after transplantation of Rbp-Jk-deficient bone marrow cells had the same NK cell phenotype as the Rbp-Jk-deleted donor mice, whereas the wild-type competitors did not. The expression of several crucial NK cell regulatory pathways was significantly altered after Rbp-Jk deletion. Together, these results demonstrate the involvement of canonical Notch signaling in regulation of multiple stages of NK cell development.</p>},
  author       = {Chaves, Patricia and Zriwil, Alya and Wittmann, Lilian and Boukarabila, Hanane and Peitzsch, Claudia and Jacobsen, Sten Eirik W. and Sitnicka, Ewa},
  issn         = {1550-6606},
  language     = {eng},
  number       = {11},
  pages        = {3307--3319},
  publisher    = {American Association of Immunologists},
  series       = {Journal of immunology (Baltimore, Md. : 1950)},
  title        = {Loss of Canonical Notch Signaling Affects Multiple Steps in NK Cell Development in Mice},
  url          = {http://dx.doi.org/10.4049/jimmunol.1701675},
  volume       = {201},
  year         = {2018},
}