Eriksson Mikael, Meadows Sarah K, Wira Charles R, Sentman Charles L
Department of Microbiology and Immunology, Dartmouth Medical School, Lebanon, NH 03756, USA.
Am J Reprod Immunol. 2006 Nov-Dec;56(5-6):321-8. doi: 10.1111/j.1600-0897.2006.00432.x.
Toll-like receptors (TLRs) recognition is an important means for the innate immune system to rapidly respond to pathogen invasion. Our aim was to determine whether uterine natural killer (uNK) cell cytokine production induced by stimulation through TLRs could be regulated by endogenous transforming growth factor (TGF)-beta in human endometrium.
Single cells were isolated from human endometrium, and interferon (IFN)-gamma production by endometrium cells and uNK cells was determined after stimulation by TLR agonists. The role of TGF-beta in regulating this response was tested by blocking TGF-beta function using antibodies or a specific inhibitor, SB431542.
TGF-beta blockade increased TLR agonist induced IFN-gamma by uNK cells. The regulation of uNK cell cytokine production was observed when uNK cells were incubated with agonists for TLR2 (PGN) or TLR3 (polyI:C). Blockade of TGF-beta or TGF-beta receptor signaling had no effect on constitutive cytokine production in the absence of TLR agonists.
The results indicate that endogenous TGF-beta alters cytokine responses of uNK cells in human endometrium in response to TLR agonists. These data suggest that uNK cell responses to microbial pathogens in the endometrium are regulated by the amount of biologically active TGF-beta present within the human endometrium.
Toll样受体（TLR）识别是先天免疫系统快速应对病原体入侵的重要方式。我们的目的是确定人子宫内膜中通过TLR刺激诱导的子宫自然杀伤（uNK）细胞细胞因子产生是否受内源性转化生长因子（TGF）-β调节。
从人子宫内膜中分离单细胞，在用TLR激动剂刺激后，测定子宫内膜细胞和uNK细胞产生的干扰素（IFN）-γ。通过使用抗体或特异性抑制剂SB431542阻断TGF-β功能来测试TGF-β在调节这种反应中的作用。
TGF-β阻断增加了uNK细胞由TLR激动剂诱导产生的IFN-γ。当uNK细胞与TLR2（肽聚糖）或TLR3（聚肌胞苷酸）激动剂孵育时，观察到了uNK细胞细胞因子产生的调节。在没有TLR激动剂的情况下，阻断TGF-β或TGF-β受体信号传导对组成性细胞因子产生没有影响。
结果表明，内源性TGF-β改变人子宫内膜中uNK细胞对TLR激动剂的细胞因子反应。这些数据表明，uNK细胞对子宫内膜中微生物病原体的反应受人类子宫内膜中存在的生物活性TGF-β量的调节。
