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Project context and summary :
Energy demands vary widely depending on cellular activation states. Here we perform an integrated bioenergetic analysis (epigenetic, transcriptomic and metabolomic) of the human CD56Br and CD56Dim natural killer (NK) cell subsets under steady-state conditions and after cytokine activation. We found that CD56Dim NK cells were metabolically active at steady state, but that both subsets increased bioenergetic properties upon priming with IL-15, with metabolic profiles similar to tonsillar NK cells. In contrast, IL-12/IL-18-induced cell activation promoted a dichotomous response with an elevated respiratory and functional capacity in CD56Br NK cells versus a metabolic switch towards glycolysis and reduced IFN-γ production in CD56Dim NK cells. The latter was associated with mitochondria fragmentation; inhibition of which increased IFN-γ production. Polarized mitochondria were identified with the CD57+ CD56Dim NK cell subset, thereby identifying a potential signature for NK cell functional maturation. We propose mitochondrial remodeling as a key regulator of NK cell function.Related team publications :
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