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

Autor:	Ma S; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA 91010.; Hematologic Malignancies Research Institute, City of Hope National Medical Center, Los Angeles, CA 91010., Tang T; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA 91010., Wu X; Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou 215123, China., Mansour AG; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA 91010., Lu T; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA 91010., Zhang J; Department of Computational and Quantitative Medicine, City of Hope National Medical Center, Los Angeles, CA 91010., Wang LS; Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226., Caligiuri MA; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA 91010; mcaligiuri@coh.org jiayu@coh.org.; Hematologic Malignancies Research Institute, City of Hope National Medical Center, Los Angeles, CA 91010.; Comprehensive Cancer Center, City of Hope, Los Angeles, CA 91010., Yu J; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA 91010; mcaligiuri@coh.org jiayu@coh.org.; Hematologic Malignancies Research Institute, City of Hope National Medical Center, Los Angeles, CA 91010.; Comprehensive Cancer Center, City of Hope, Los Angeles, CA 91010.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2022 Jan 18; Vol. 119 (3).
DOI:	10.1073/pnas.2114134119
Abstrakt:	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. Competing Interests: The authors declare no competing interest. (Copyright © 2022 the Author(s). Published by PNAS.)
Databáze:	MEDLINE
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