Dendritic cells support the in vivo development and maintenance of NK cells via IL-15 trans-presentation.
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-gamma 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.
Castillo
Eliseo F
EF
Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Stonier
Spencer W
SW
Frasca
Loredana
L
Schluns
Kimberly S
KS
D019264:Adoptive Transfer; D000818:Animals; D039521:CD11c Antigen / Q000276:immunology / Q000378:metabolism; D015550:Cell Degranulation / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D019409:Interleukin-15 / Q000276:immunology* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055650:NK Cell Lectin-Like Receptor Subfamily A / Q000276:immunology / Q000378:metabolism; D053647:Receptors, Interleukin-15 / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D039521:CD11c Antigen; C508025:Il15ra protein, mouse; D019409:Interleukin-15; D055650:NK Cell Lectin-Like Receptor Subfamily A; D053647:Receptors, Interleukin-15; D007371:Interferon-gamma