Interaction between dendritic cells and natural killer cells during pregnancy in mice
Interaction between dendritic cells and natural killer cells during pregnancy in mice
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DOI：
10.1007/s00109-008-0342-2
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发表时间：
2008-07-01
影响因子：
4.7
通讯作者：
Arck, Petra C.
中科院分区：
文献类型：
--
作者：
Blois, Sandra M.;Barrientos, Gabriela;Arck, Petra C.
母胎界面先天性和适应性免疫反应的复杂调节促进了携带父源抗原的滋养层细胞的耐受性。这种调节功能涉及子宫树突状细胞（uDC）和自然杀伤（uNK）细胞。 NK 和 DC“串扰”的存在已在各种实验环境中得到揭示；其生物学意义从协同刺激到细胞裂解。关于母胎界面处 NK 和 DC 串扰的存在或作用知之甚少。本研究表明，小鼠 NK 和 DC 的相互作用在体外受到滋养层细胞的调节。这种相互作用促进了耐受性微环境，其特征是 uNK 细胞和 uDC 上激活标记物的表达下调以及 Th2 细胞因子的优势。 NK 和 DC 的相互作用也会影响子宫细胞增殖，并且该过程将受到滋养层衍生信号的强烈调节。的确;虽然在允许子宫细胞和滋养层直接接触的常规共培养中观察到低增殖率，但在 Transwell 培养系统中孵育显着增加了子宫细胞增殖，这表明可溶性因子是小鼠妊娠建立期间母体和概念之间分子“对话”的关键介质。我们的数据进一步表明，在高流产小鼠交配中，与耐受诱导相关的滋养层细胞的调节功能受到损害。有趣的是，我们观察到 uDC 分泌的 interleukin-12p70 在 uNK 细胞存在时显着消除。总而言之，我们的结果提供了第一个证据，证明小鼠母胎界面处涉及 NK 细胞、DC 和滋养层的相互作用的微妙平衡支持成功的妊娠结局。
A complex regulation of innate and adaptive immune responses at the maternal fetal interface promotes tolerance of trophoblast cells carrying paternally derived antigens. Such regulatory functions involve uterine dendritic cells (uDC) and natural killer (uNK) cells. The existence of a NK and DC "cross talk" has been revealed in various experimental settings; its biological significance ranging from cooperative stimulation to cell lysis. Little is known about the presence or role of NK and DC cross talk at the maternal fetal interface. The present study shows that mouse NK and DC interactions are subject to modulation by trophoblast cells in vitro. This interaction promotes a tolerogenic microenvironment characterized by downregulation of the expression of activation markers on uNK cells and uDC and dominance of Th2 cytokines. NK and DC interactions would also influence uterine cell proliferation and this process would be strongly modulated by trophoblast-derived signals. Indeed; while low proliferation rates were observed upon regular coculture allowing direct contact between uterine cells and trophoblasts, incubation in a transwell culture system markedly increased uterine cell proliferation suggesting that soluble factors are key mediators in the molecular "dialog" between the mother and the conceptus during the establishment of mouse pregnancy. Our data further reveal that the regulatory functions of trophoblast cells associated with tolerance induction are impaired in high abortion murine matings. Interestingly, we observed that secretion of interleukin-12p70 by uDC is dramatically abrogated in the presence of uNK cells. Taken together, our results provide the first evidence that a delicate balance of interactions involving NK cells, DC, and trophoblasts at the mouse maternal fetal interface supports a successful pregnancy outcome.