PDGF-D-PDGFR beta signaling enhances IL-15-mediated human natural killer cell survival

The axis of platelet-derived growth factor (PDGF) and PDGF receptor-beta (PDGFR beta) plays prominent roles in cell growth and motility. In addition, PDGF-D enhances human natural killer (NK) cell effector functions when binding to the NKp44 receptor. Here, we report an additional but previously unknown role of PDGF-D, whereby it mediates interleukin-15 (IL-15)-induced human NK cell survival but not effector functions via its binding to PDGFR beta but independent of its binding to NKp44. Resting NK cells express no PDGFR beta and only a low level of PDGF-D, but both are significantly up-regulated by IL-15, via the nuclear factor kappa B signaling pathway, to promote cell survival in an autocrine manner. Both ectopic and IL-15-induced expression of PDGFR beta improves NK cell survival in response to treatment with PDGF-D. Our results suggest that the PDGF-D-PDGFR beta signaling pathway is a mechanism by which IL-15 selectively regulates the survival of human NK cells without modulating their effector functions.