Central role of interleukin-15 in postovulatory recruitment of peripheral blood CD16(-) natural killer cells into human endometrium

Central role of interleukin-15 in postovulatory recruitment of peripheral blood CD16(-) natural killer cells into human endometrium
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DOI:
10.1210/jc.2004-2447
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发表时间:
2005-05-01
影响因子:
5.8
通讯作者:
Honjo, H
Honjo, H
中科院分区:
医学2区
文献类型:
--
作者:
Kitaya, K;Yamaguchi, T;Honjo, H

文献摘要

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排卵后,人子宫内膜中出现大量的CD 16(-)自然杀伤(NK)细胞。这种现象的一个可能的解释是从外周血(PB)CD 16(-)NK细胞募集。在这项研究中,我们研究了IL-15是否参与排卵后从PB CD 16(-)NK细胞的募集。IL-15受体α链在PB CD 16(-)NK细胞上表达,但在CD 16(+)NK细胞上不表达。在体外迁移试验中,重组人IL-15富集了PBCD 16(-)NK细胞。分泌期子宫内膜可溶性蛋白组分也富集这些NK细胞,但增殖期子宫内膜可溶性蛋白组分不富集这些NK细胞。用抗IL-15单克隆抗体中和分泌期子宫内膜中的IL-15可显著降低PB CD 16(-)NK细胞的富集。相比之下,其他潜在的趋化因子,包括基质细胞衍生因子-1或巨噬细胞炎性蛋白-1 α的中和,没有显着的效果。子宫内膜可溶性蛋白组分中IL-15浓度在分泌期高于增殖期,在分泌中期达到峰值。这些结果支持了分泌期子宫内膜中内源性IL-15在排卵后PB CD 16(-)NK细胞向人子宫内膜募集中起核心作用的观点。
A large number of CD16(-) natural killer (NK) cells appear in the human endometrium after ovulation. One possible explanation for this phenomenon is recruitment from peripheral blood (PB) CD16(-) NK cells. In this study, we examined whether IL-15 is involved in postovulatory recruitment from PB CD16(-) NK cells. The IL-15 receptor alpha chain was expressed on PB CD16(-) NK cells but not on CD16(+) NK cells. In an in vitro migration assay, recombinant human IL-15 enriched PBCD16( -) NK cells. Endometrial soluble protein fraction in the secretory phase, but not in the proliferative phase, also enriched these NK cells. Neutralization of IL-15 in the secretory phase endometrium with anti-IL-15 monoclonal antibody significantly lowered the enrichment of PB CD16(-) NK cells. In contrast, neutralization of other potential chemokines, including stromal cell-derived factor-1 or macrophage inflammatory protein-1 alpha, had no significant effect. The IL-15 concentration in the endometrial soluble protein fraction was higher in the secretory phase than in the proliferative phase, with a peak in the midsecretory phase. These results support the idea that endogenous IL-15 in secretory phase endometrium plays a central role in postovulatory recruitment of PB CD16(-) NK cells into the human endometrium.