RT Journal Article
SR Electronic
T1 Short-term IL-15 priming leaves a long-lasting signalling imprint in mouse NK cells independently of a metabolic switch
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202000723
DO 10.26508/lsa.202000723
VO 4
IS 4
A1 Thuy T Luu
A1 Laurent Schmied
A1 Ngoc-Anh Nguyen
A1 Clotilde Wiel
A1 Stephan Meinke
A1 Dara K Mohammad
A1 Martin Bergö
A1 Evren Alici
A1 Nadir Kadri
A1 Sridharan Ganesan
A1 Petter Höglund
YR 2021
UL https://www.life-science-alliance.org/content/4/4/e202000723.abstract
AB 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.