TLRs mediate IFN-γ production by human uterine NK cells in endometrium
TLRs mediate IFN-γ production by human uterine NK cells in endometrium
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DOI：
10.4049/jimmunol.176.10.6219
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发表时间：
2006-05-15
影响因子：
4.4
通讯作者：
Sentman, Charles L.
中科院分区：
文献类型：
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作者：
Eriksson, Mikael;Meadows, Sarah K.;Sentman, Charles L.
人子宫内膜（EM）含有巨噬细胞、NK细胞、T细胞、B细胞和与各种基质细胞和上皮细胞接触的嗜中性粒细胞。这些不同细胞类型之间的相互作用及其在防御病原体入侵中的作用对于控制感染和繁殖非常重要。TLR是能够识别保守的病原体相关分子模式的受体家族。在这项研究中，我们确定了从人类EM子宫NK细胞（uNK）的TLR的表达和uNK细胞对TLR激动剂刺激的反应程度。当用TLR 2或TLR 3的激动剂（分别为肽聚糖或聚（I：C））刺激总的人子宫内膜细胞时，uNK细胞表达TLR 2、3和4，并产生IFN-γ。活化的uNK细胞克隆在用肽聚糖或poly（I：C）刺激后产生IFN-γ。然而，纯化的uNK细胞没有直接响应TLR激动剂，但IFN-γ产生的uNK细胞在TLR刺激时，与AM共培养。这些数据表明，uNK细胞表达TLR，并且它们可以通过产生IFN-γ对EM内的TLR激动剂作出应答。这些数据还表明，uNK细胞不直接响应TLR刺激，而是其IFN-γ的产生取决于与EM内其他细胞的相互作用。
The hum-an endometrium (EM) contains macrophages, NK cells, T cells, B cells, and neutrophils in contact with a variety of stromal and epithelial cells. The interplay between these different cell types and their roles in defense against pathogen invasion in this specialized tissue are important for controlling infection and reproduction. TLRs are a family of receptors able to recognize conserved pathogen-associated molecular patterns. In this study, we determined the expression of TLRs on uterine NK (uNK) cells from the human EM and the extent to which uNK cells responded to TLR agonist stimulation. uNK cells expressed TLRs 2, 3, and 4, and produced IFN-gamma when total human endometrial cells were stimulated with agonists to TLR2 or TLR3 (peptidoglyean or poly(I:C), respectively). Activated uNK cell clones produced IFN-gamma upon stimulation with peptidoglycan or poly(I:C). However, purified uNK cells did not respond directly to TLR agonists, but IFN-gamma was produced by uNK cells in response to TLR stimulation when cocultured with AM. These data indicate that uNK cells express TLRs and that they can respond to TLR agonists within EM by producing IFN-gamma. These data also indicate that the uNK cells do not respond directly to TLR stimulation, but rather their production of IFN-gamma is dependent upon interactions with other cells within EM.