HLA-G homodimer-induced cytokine secretion through HLA-G receptors on human decidual macrophages and natural killer cells
HLA-G homodimer-induced cytokine secretion through HLA-G receptors on human decidual macrophages and natural killer cells
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DOI：
10.1073/pnas.0901173106
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发表时间：
2009-04-07
影响因子：
11.1
通讯作者：
Strominger, Jack L.
中科院分区：
文献类型：
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作者：
Li, Changlin;Houser, Brandy L.;Strominger, Jack L.
从早期妊娠终止后获得的材料中分离出人蜕膜CD14（+）巨噬细胞和CD56(+) NK细胞。每种细胞类型都表达组织相容性白细胞抗原(HLA)-G（一种MHC类Ib蛋白，表达于上皮外滋养细胞上）的特异性表面受体，CD14（+）巨噬细胞上的LILRB1和CD56(+) NK细胞上的KIR2DL4。与抗lilrb1或抗kir2dl4交联导致一小部分mrna上调，包括使用代表114种细胞因子的微阵列检测到的IL-6、IL-8和TNF - α。与表达HLA-G同型二聚体的转染物孵育（而不是与表达HLA-G单体的转染物孵育）导致两组白细胞分泌相同的细胞因子蛋白。此外，两组白细胞的细胞因子分泌均被适当的抗受体mAb和抗hla - g阻断。巨噬细胞分泌这些细胞因子的量明显大于NK细胞分泌的量。两种细胞均组成性分泌VEGF。LILRB1包含一个基于酪氨酸的免疫受体开关基序，在这里作为激活受体起作用，尽管它被称为抑制受体。KIR2DL4也作为激活受体发挥作用，尽管它也可能作为抑制受体发挥作用。促炎和促血管生成蛋白的分泌支持这些白细胞在重要过程中的作用，这些过程对成功怀孕至关重要，但它们可能只代表分泌的蛋白质的一部分。
Human decidual CD14(+) macrophages and CD56(+) NK cells were isolated from material obtained after first-trimester pregnancy terminations. Each cell type expressed a specific surface receptor for histocompatibility leukocyte antigen (HLA)-G (an MHC class Ib protein that is expressed on extravillous trophoblasts), LILRB1 on CD14(+) macrophages and KIR2DL4 on CD56(+) NK cells. Cross-linking with anti-LILRB1 or anti-KIR2DL4 resulted in up-regulation of a small subset of mRNAs including those for IL-6, IL-8, and TNF alpha detected using a microarray representing 114 cytokines. Incubation with transfectants expressing the HLA-G homodimer (but not with transfectants expressing the HLA-G monomer) resulted in secretion of the same cytokine proteins from both leukocyte sets. Moreover, cytokine secretion from both leukocyte sets was blocked by both the appropriate anti-receptor mAb and by anti-HLA-G. The amount of these cytokines secreted by decidual macrophages was substantially greater than that secreted by decidual NK cells. VEGF was constitutively secreted by both cell types. LILRB1, which contains an immunoreceptor tyrosine-based switch motif, functions here as an activating receptor, although it has been known as an inhibitory receptor. KIR2DL4 also functions as an activating receptor, although it also has the potential to function as an inhibitory receptor. Secretion of proinflammatory and proangiogenic proteins supports a role for these leukocytes in important processes that are essential for successful pregnancy, but they may represent only a portion of the proteins that are secreted.