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  2. PDGF-D-PDGFRβ signaling enhances IL-15-mediated human natural killer cell survival

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

  • Proc Natl Acad Sci U S A. 2022 Jan 18;119(3):e2114134119. doi: 10.1073/pnas.2114134119.
Shoubao Ma 1 2 Tingting Tang 1 Xiaojin Wu 3 Anthony G Mansour 1 Ting Lu 1 Jianying Zhang 4 Li-Shu Wang 5 Michael A Caligiuri 6 2 7 Jianhua Yu 6 2 7
Affiliations

Affiliations

  • 1 Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA 91010.
  • 2 Hematologic Malignancies Research Institute, City of Hope National Medical Center, Los Angeles, CA 91010.
  • 3 Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou 215123, China.
  • 4 Department of Computational and Quantitative Medicine, City of Hope National Medical Center, Los Angeles, CA 91010.
  • 5 Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226.
  • 6 Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA 91010; [email protected] [email protected]
  • 7 Comprehensive Cancer Center, City of Hope, Los Angeles, CA 91010.
Abstract

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.

Keywords

IL-15; NK cells; PDGF-D; PDGFRβ; cell survival.

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