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
  • 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.
PMID: 35027451 DOI: 10.1073/pnas.2114134119
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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