Li Zhong-Yin, Song Zhi-Hui, Meng Chao-Yang, Yang Dan-Dan, Yang Ying, Peng Jing-Pian
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, P.R. China.
University of Chinese Academy of Sciences, Beijing, P.R. China.
Sci Rep. 2015 Dec 11;5:18159. doi: 10.1038/srep18159.
We have previously shown that interferon gamma (IFN-γ) induces aberrant CD49b(+) natural killer (NK) cell recruitment by regulating CX3CL1 and eventually provokes foetal loss. In this study, we show that IFN-γ also modulates Ly-49 receptors on NK cells during pregnancy failure. The percentages of Ly-49A(+) and Ly-49G2(+) NK cells in the uteri of the IFN-γ-treated group were significantly lower than those observed in the control group. Moreover, the median fluorescence intensity (MFI) values of Ly-49A and Ly-49G2 expression on NK cells in the uteri of the IFN-γ-treated group were significantly lower than those of the control group. Using isolated spleen leucocytes, we further found that IFN-γ significantly reduced the percentage of Ly-49A(+) NK cells in vitro. However, CX3CL1 was not involved in the modulation of Ly-49 receptors, and the expression of CX3CR1 was not regulated by IFN-γ in spleen leucocytes. Collectively, our data indicate that IFN-γ can modulate Ly-49 receptors on NK cells and this process may play a role in IFN-γ-induced pregnancy failure. Thus, we provide a new line of evidence correlating the deleterious effects of IFN-γ with its role in regulating NK cell Ly-49 receptors during pregnancy failure.
我们之前已经表明,干扰素γ(IFN-γ)通过调节CX3CL1诱导异常的CD49b(+)自然杀伤(NK)细胞募集,并最终引发胎儿丢失。在本研究中,我们表明IFN-γ在妊娠失败期间也会调节NK细胞上的Ly-49受体。IFN-γ处理组子宫中Ly-49A(+)和Ly-49G2(+) NK细胞的百分比显著低于对照组。此外,IFN-γ处理组子宫中NK细胞上Ly-49A和Ly-49G2表达的中位荧光强度(MFI)值显著低于对照组。使用分离的脾脏白细胞,我们进一步发现IFN-γ在体外显著降低了Ly-49A(+) NK细胞的百分比。然而,CX3CL1不参与Ly-49受体的调节,并且脾脏白细胞中CX3CR1的表达不受IFN-γ的调控。总体而言,我们的数据表明IFN-γ可以调节NK细胞上的Ly-49受体,并且这一过程可能在IFN-γ诱导的妊娠失败中起作用。因此,我们提供了新的证据,将IFN-γ的有害作用与其在妊娠失败期间调节NK细胞Ly-49受体的作用联系起来。