Signaling networks modulating NK cell memory
NKG2C+ natural killer (NK) cells exhibit a high degree of oligoclonality in human cytomegalovirus-seropositive individuals.
TNFα–TNFR2 signaling provides a critical co-stimulatory signal that enhances NK cell effector function and sustains cellular proliferation.
Homeostatic and proinflammatory cytokines activate STAT- and NF-κB dependent transcriptional programs that remodel chromatin at effector gene loci such as Ifng, drive metabolic fitness, and enhance NK cell expansion.
CIS and CREM operate as negative feedback regulators to tune the amplitude of interleukin-15–STAT5-mediated NK cell activation and represent potential therapeutic targets.
Crosstalk between the three signals of receptor engagement, co-stimulation, and cytokine signaling orchestrates transcriptional programs, epigenetic imprinting, and metabolic rewiring that collectively define the quality, quantity, longevity, and adaptability of NK cells.
https://www.cell.com/trends/immunology/fulltext/S1471-4906(26)00012-8
