Stage-Specific Requirement for Eomes in Mature NK Cell Homeostasis and Cytotoxicity.
Animals
Antigens, Ly
/ genetics
Apoptosis
Cell Cycle Checkpoints
Histocompatibility Antigens Class I
/ genetics
Killer Cells, Natural
/ cytology
Mice
Mice, Inbred C57BL
Mice, Knockout
Natural Cytotoxicity Triggering Receptor 1
/ genetics
Receptors, Interleukin-15
/ metabolism
STAT5 Transcription Factor
/ metabolism
Signal Transduction
Spleen
/ cytology
T-Box Domain Proteins
/ deficiency
Eomes
NK cell
Ncr1-specific
cytotoxicity
homeostasis
in vivo
inducible-cre model
innate lymphoid cell
maturation
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
02 06 2020
02 06 2020
Historique:
received:
20
11
2019
revised:
29
04
2020
accepted:
11
05
2020
entrez:
4
6
2020
pubmed:
4
6
2020
medline:
4
5
2021
Statut:
ppublish
Résumé
Natural killer (NK) cells are cytotoxic innate lymphoid cells (ILCs) that mediate antiviral and antitumor responses and require the transcriptional regulator Eomesodermin (Eomes) for early development. However, the role of Eomes and its molecular program in mature NK cell biology is unclear. To address this, we develop a tamoxifen-inducible, type-1-ILC-specific (Ncr1-targeted) cre mouse and combine this with Eomes-floxed mice. Eomes deletion after normal NK cell ontogeny results in a rapid loss of NK cells (but not ILC1s), with a particularly profound effect on penultimately mature stage III NK cells. Mechanisms responsible for stage III reduction include increased apoptosis and impaired maturation from stage II precursors. Induced Eomes deletion also decreases NK cell cytotoxicity and abrogates in vivo rejection of major histocompatibility complex (MHC)-class-I-deficient cells. However, other NK cell functional responses, and stage IV NK cells, are largely preserved. These data indicate that mature NK cells have distinct Eomes-dependent and -independent stages.
Identifiants
pubmed: 32492428
pii: S2211-1247(20)30697-5
doi: 10.1016/j.celrep.2020.107720
pmc: PMC7265846
pii:
doi:
Substances chimiques
Antigens, Ly
0
Eomes protein, mouse
0
Histocompatibility Antigens Class I
0
Natural Cytotoxicity Triggering Receptor 1
0
Ncr1 protein, mouse
0
Receptors, Interleukin-15
0
STAT5 Transcription Factor
0
T-Box Domain Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
107720Subventions
Organisme : NCI NIH HHS
ID : F32 CA200253
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA171963
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA205239
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI102924
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007200
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007088
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA210084
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NCI NIH HHS
ID : K12 CA167540
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA091842
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI127752
Pays : United States
Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.