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

Dendritic cells support the in vivo development and maintenance of NK cells via IL-15 trans-presentation.
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DOI:
10.4049/jimmunol.0900719
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发表时间:
2009-10-15
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Schluns KS
Schluns KS
中科院分区:
其他
文献类型:
--
作者:
Castillo EF;Stonier SW;Frasca L;Schluns KS

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IL-15是调节NK细胞发育和动态平衡的关键成分,通过一种称为反式递呈的机制递送。在发育过程中,必须进行多项活动,以产生对肿瘤和病毒免疫至关重要的功能成熟的NK细胞群。然而,IL-15如何调节这些不同的事件,以及更重要的是,哪些细胞向NK细胞提供IL-15来驱动这些事件,目前尚不清楚。已知树突状细胞(DC)可通过IL-15反式递呈激活NK细胞,但DC利用IL-15反式递呈促进NK细胞的发育和维持体内平衡的能力尚未确立。在目前的研究中,我们发现单独由CD11c+细胞反式递呈IL-15有助于体内NK细胞的发育和维持。更具体地说,DC介导的IL-15反式递呈促进了NK细胞的分化,其中包括激活和抑制Ly49受体的上调。虽然这些细胞不具有成熟的CD11b高表型,但它们能够在类似于野生型NK细胞的刺激下脱颗粒并产生干扰素-γ。此外,DC通过在外周反式递呈IL-15促进成熟NK细胞的存活。因此,已经确定了NK-DC相互作用的另一个作用,即DC支持NK细胞的发育和动态平衡。
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 CD11bhigh 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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