Dendritic cells support the in vivo development and maintenance of NK cells via IL-15 trans-presentation

EF Castillo, SW Stonier, L Frasca… - The Journal of …, 2009 - journals.aai.org
EF Castillo, SW Stonier, L Frasca, KS Schluns
The Journal of Immunology, 2009journals.aai.org
IL-15 is a key component that regulates the development and homeostasis of NK cells and is
delivered through a mechanism termed trans-presentation. During development, multiple
events must proceed to generate a functional mature population of NK cells that are vital for
tumor and viral immunity. Nevertheless, how IL-15 regulates these various events and more
importantly what cells provide IL-15 to NK cells to drive these events is unclear. It is known
dendritic cells (DC) can activate NK cells via IL-15 trans-presentation; however, the ability of …
Abstract
IL-15 is a key component that regulates the development and homeostasis of NK cells and is delivered through a mechanism termed trans-presentation. During development, multiple events must proceed to generate a functional mature population of NK cells that are vital for tumor and viral immunity. Nevertheless, how IL-15 regulates these various events and more importantly what cells provide IL-15 to NK cells to drive these events is unclear. It is known dendritic cells (DC) can activate NK cells via IL-15 trans-presentation; however, the ability of DC to use IL-15 trans-presentation to promote the development and homeostatic maintenance of NK cell has not been established. In this current study, we show that IL-15 trans-presentation solely by CD11c+ cells assists the in vivo development and maintenance of NK cells. More specifically, DC-mediated IL-15 trans-presentation drove the differentiation of NK cells, which included the up-regulation of the activating and inhibitory Ly49 receptors. Although these cells did not harbor a mature CD11b high phenotype, they were capable of degranulating and producing IFN-γ upon stimulation similar to wild-type NK cells. In addition, DC facilitated the survival of mature NK cells via IL-15 trans-presentation in the periphery. Thus, an additional role for NK-DC interactions has been identified whereby DC support the developmental and homeostatic niche of NK cells.
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