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

Research output: Contribution to journalArticle

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 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.

Details

Authors
  • Patricia Chaves
  • Alya Zriwil
  • Lilian Wittmann
  • Hanane Boukarabila
  • Claudia Peitzsch
  • Sten Eirik W. Jacobsen
  • Ewa Sitnicka
Organisations
External organisations
  • University of Oxford
  • Karolinska University Hospital
  • Karolinska Institutet
  • Lund University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Immunology in the medical area
Original languageEnglish
Pages (from-to)3307-3319
Number of pages13
JournalJournal of immunology (Baltimore, Md. : 1950)
Volume201
Issue number11
Publication statusPublished - 2018
Publication categoryResearch
Peer-reviewedYes