Short-term IL-15 priming leaves a long-lasting signalling imprint in mouse NK cells independently of a metabolic switch.
Animals
Biomarkers
Cytokines
/ metabolism
Energy Metabolism
Immunophenotyping
Interferon-gamma
/ metabolism
Interleukin-15
/ metabolism
Interleukin-2
/ metabolism
Killer Cells, Natural
/ drug effects
Lymphocyte Activation
Mice
Phosphorylation
Reactive Oxygen Species
/ metabolism
Signal Transduction
/ drug effects
Journal
Life science alliance
ISSN: 2575-1077
Titre abrégé: Life Sci Alliance
Pays: United States
ID NLM: 101728869
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
received:
31
03
2020
revised:
22
01
2021
accepted:
25
01
2021
entrez:
17
2
2021
pubmed:
18
2
2021
medline:
5
10
2021
Statut:
epublish
Résumé
IL-15 priming of NK cells is a broadly accepted concept, but the dynamics and underlying molecular mechanisms remain poorly understood. We show that as little as 5 min of IL-15 treatment in vitro, followed by removal of excess cytokines, results in a long-lasting, but reversible, augmentation of NK cell responsiveness upon activating receptor cross-linking. In contrast to long-term stimulation, improved NK cell function after short-term IL-15 priming was not associated with enhanced metabolism but was based on the increased steady-state phosphorylation level of signalling molecules downstream of activating receptors. Inhibition of JAK3 eliminated this priming effect, suggesting a cross talk between the IL-15 receptor and ITAM-dependent activating receptors. Increased signalling molecule phosphorylation levels, calcium flux, and IFN-γ secretion lasted for up to 3 h after IL-15 stimulation before returning to baseline. We conclude that IL-15 rapidly and reversibly primes NK cell function by modulating activating receptor signalling. Our findings suggest a mechanism by which NK cell reactivity can potentially be maintained in vivo based on only brief encounters with IL-15 trans-presenting cells.
Identifiants
pubmed: 33593878
pii: 4/4/e202000723
doi: 10.26508/lsa.202000723
pmc: PMC7918643
pii:
doi:
Substances chimiques
Biomarkers
0
Cytokines
0
Interleukin-15
0
Interleukin-2
0
Reactive Oxygen Species
0
Interferon-gamma
82115-62-6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2021 Luu et al.
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