Effect of TLR3 and TLR7 activation in uterine NK cells from non-obese diabetic (NOD) mice
Effect of TLR3 and TLR7 activation in uterine NK cells from non-obese diabetic (NOD) mice
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TLR3 和 TLR7 激活对非肥胖糖尿病 (NOD) 小鼠子宫 NK 细胞的影响。
DOI：
10.1016/j.jri.2009.03.004
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发表时间：
2009-10-01
影响因子：
3.4
通讯作者：
Saito, Shigeru
中科院分区：
文献类型：
--
作者：
Lin, Yi;Ren, Lingling;Saito, Shigeru
Toll样受体（TLR） - TLR相互作用被认为在TLR信号传导中具有重要作用。在此，我们研究了特异性TLR3和TLR7激动剂聚肌苷酸 - 聚胞苷酸（poly (I:C)）和R837单独及联合使用对子宫免疫细胞功能的影响，以及它们随后对妊娠结局的影响。采用非肥胖糖尿病（NOD）小鼠×C57BL/6以及野生型BALB/c×C57BL/6模型的同种异体妊娠。用聚肌苷酸 - 聚胞苷酸和R837诱导后，观察到胚胎吸收率增加，并且与子宫中产生肿瘤坏死因子 - α（TNF - α）和干扰素 - γ（IFN - γ）的CD45⁺细胞数量增加有关。进一步检查表明，虽然在BALB/c小鼠的CD3⁺细胞和CD49b⁺细胞中均检测到细胞因子表达，但NOD小鼠细胞的表现不同。在NOD小鼠中，细胞因子表达升高归因于CD3⁺ T细胞，在CD49b⁺自然杀伤（NK）细胞中未检测到反应。联合激动剂的累加效应被c - Jun氨基末端激酶（JNK）丝裂原活化蛋白激酶（MAPK）抑制剂SP600125部分抑制，并几乎被细胞外信号调节激酶（ERK）MAPK抑制剂PD98059完全消除。这些结果表明，在NOD小鼠中，增加的TLR3和TLR7信号是通过Th1型T细胞而非NK细胞传递的。此外，ERK MAPK途径在TLR3和TLR7信号传导中可能至关重要。（C）2009爱思唯尔爱尔兰有限公司。保留所有权利。
Toll-like receptor (TLR)-TLR cross talk is thought to be important in TLR signaling. Herein, we investigated the effect of specific TLR3 and TLR7 agonists, poly (I:C) and R837, individually and in combination, on uterine immune cell function and their subsequent effects on pregnancy outcome. Allogeneic pregnancies in the non-obese diabetic (NOD) mouse x C57BL/6 and wild-type BALB/c x C57BL/6 model were used. An additive increase in embryo resorption was observed after induction with both poly (I:Q and R837, and was associated with elevated numbers of both TNF-alpha- and IFN-gamma-producing CD45(+) cells in the uterus. Further examination showed that while cytokine expression was detected in both CD3(+) cells and CD49b(+) cells in BALB/c mice, NOD mouse cells behaved differently. In NOD mice, elevated cytokine expression was attributed to CD3(+) T cells, with no response detected in the CD49b(+) NK cells. The additive effect of combined agonists was partially inhibited by the Jun N-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) inhibitor SP600125 and almost completely abrogated by the extracellular signal-regulated kinase (ERK) MAPK inhibitor PD98059. These results suggest that increased TLR3 and TLR7 signals are transmitted via Th1-type T cells, rather than NK cells, in NOD mice. Furthermore, the ERK MAPK pathway may be critical in TLR3 and TLR7 signaling. (C) 2009 Elsevier Ireland Ltd. All rights reserved.