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Short-term IL-15 pr...
Short-term IL-15 priming leaves a long-lasting signalling imprint in mouse NK cells independently of a metabolic switch
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Luu, TT (author)
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Schmied, L (author)
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Nguyen, NA (author)
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Wiel, C (author)
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- Meinke, S (author)
- Karolinska Institutet
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- Mohammad, DK (author)
- Karolinska Institutet
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- Bergo, M (author)
- Karolinska Institutet
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- Alici, E (author)
- Karolinska Institutet
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- Kadri, N (author)
- Karolinska Institutet
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Ganesan, S (author)
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- Hoglund, P (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2021-02-16
- 2021
- English.
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In: Life science alliance. - : Life Science Alliance, LLC. - 2575-1077. ; 4:4
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https://www.life-sci...
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http://kipublication...
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https://doi.org/10.2...
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Abstract
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- 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.
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- art (subject category)
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- By the author/editor
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Luu, TT
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Schmied, L
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Nguyen, NA
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Wiel, C
-
Meinke, S
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Mohammad, DK
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show more...
-
Bergo, M
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Alici, E
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Kadri, N
-
Ganesan, S
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Hoglund, P
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show less...
- Articles in the publication
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Life science all ...
- By the university
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Karolinska Institutet