Keap1-Nrf2 System Plays an Important Role in Invariant Natural Killer T Cell Development and Homeostasis.
Animals
Cell Differentiation
Cell Proliferation
Cell Survival
Glucose
/ metabolism
Glucose Transporter Type 1
/ genetics
Interleukin-2 Receptor beta Subunit
/ genetics
Kelch-Like ECH-Associated Protein 1
/ deficiency
Mice
Mice, Inbred C57BL
Mice, Knockout
NF-E2-Related Factor 2
/ deficiency
Natural Killer T-Cells
/ cytology
Proto-Oncogene Proteins c-bcl-2
/ genetics
Reactive Oxygen Species
/ metabolism
Thymus Gland
/ metabolism
NKT cells
antioxidant system
cell metabolism
innate T cells
reactive oxygen species
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
16 04 2019
16 04 2019
Historique:
received:
06
09
2018
revised:
02
01
2019
accepted:
13
03
2019
entrez:
18
4
2019
pubmed:
18
4
2019
medline:
17
6
2020
Statut:
ppublish
Résumé
Kelch-like ECH-associated protein 1 (Keap1) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) proteins work in concert to regulate the levels of reactive oxygen species (ROS). The Keap1-Nrf2 antioxidant system also participates in T cell differentiation and inflammation, but its role in innate T cell development and functions remains unclear. We report that T cell-specific deletion of Keap1 results in defective development and reduced numbers of invariant natural killer T (NKT) cells in the thymus and the peripheral organs in a cell-intrinsic manner. The frequency of NKT2 and NKT17 cells increases while NKT1 decreases in these mice. Keap1-deficient NKT cells show increased rates of proliferation and apoptosis, as well as increased glucose uptake and mitochondrial function, but reduced ROS, CD122, and Bcl2 expression. In NKT cells deficient in Nrf2 and Keap1, all these phenotypic and metabolic defects are corrected. Thus, the Keap1-Nrf2 system contributes to NKT cell development and homeostasis by regulating cell metabolism.
Identifiants
pubmed: 30995469
pii: S2211-1247(19)30382-1
doi: 10.1016/j.celrep.2019.03.052
pmc: PMC6743333
mid: NIHMS1049435
pii:
doi:
Substances chimiques
Glucose Transporter Type 1
0
Interleukin-2 Receptor beta Subunit
0
Keap1 protein, mouse
0
Kelch-Like ECH-Associated Protein 1
0
NF-E2-Related Factor 2
0
Proto-Oncogene Proteins c-bcl-2
0
Reactive Oxygen Species
0
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
699-707.e4Subventions
Organisme : NIAID NIH HHS
ID : R01 AI121156
Pays : United States
Informations de copyright
Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
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