PDGF-D-PDGFRβ signaling enhances IL-15-mediated human natural killer cell survival.
Shoubao MaTingting TangXiaojin WuAnthony G MansourTing LuJianying ZhangLi-Shu WangMichael A CaligiuriJian Hua YuPublished in: Proceedings of the National Academy of Sciences of the United States of America (2022)
The axis of platelet-derived growth factor (PDGF) and PDGF receptor-beta (PDGFRβ) 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 PDGFRβ but independent of its binding to NKp44. Resting NK cells express no PDGFRβ and only a low level of PDGF-D, but both are significantly up-regulated by IL-15, via the nuclear factor κB signaling pathway, to promote cell survival in an autocrine manner. Both ectopic and IL-15-induced expression of PDGFRβ improves NK cell survival in response to treatment with PDGF-D. Our results suggest that the PDGF-D-PDGFRβ signaling pathway is a mechanism by which IL-15 selectively regulates the survival of human NK cells without modulating their effector functions.
Keyphrases
- nk cells
- endothelial cells
- smooth muscle
- signaling pathway
- vascular smooth muscle cells
- growth factor
- nuclear factor
- high glucose
- pluripotent stem cells
- induced pluripotent stem cells
- dendritic cells
- epithelial mesenchymal transition
- regulatory t cells
- poor prognosis
- pi k akt
- induced apoptosis
- blood pressure
- oxidative stress
- pseudomonas aeruginosa
- cystic fibrosis
- binding protein
- staphylococcus aureus
- combination therapy