可溶性HLA-G上调蜕膜免疫细胞NK细胞受体的表达

Soluble HLA-G up-regulates the expression of natural killer receptors on the decidual immune cells

sHLA-G是妊娠期特异的免疫抑制分子,在受孕子宫及妊娠期女性外周血中含量丰富,提示其在维持母胎耐受中发挥重要作用。我们前期研究发现:早期难免流产病人组蜕膜组织KIR2DL4、ILT-2、ILT-4分子表达的水平明显低于正常妊娠对照组。为进一步分析这些抑制性受体表达下降与sHLA-G是否存在联系,我们对sHLA-G与蜕膜组织免疫细胞NKR表达的关系进行了研究。我们将不同量的sHLA-G1、sHLA-G2蛋白加至蜕膜单个核细胞悬液、外周血单个核细胞悬液及NK92细胞株中,分别孵育12h、24h、48h后,用Real-Time RT-PCR、FACS对NKR的表达进行检测。研究发现sHLA-G可以不同程度地上调蜕膜单个核细胞、外周血单个核细胞、NK92细胞表面ILT-2、ILT-4、KIR2DL4的表达。这个发现让我们对sHLA-G诱导免疫耐受的机制有了更深的认识。sHLA-G上调抑制性受体表达这一作用具有重要生理意义,它可以抑制效应细胞的杀伤功能,使母胎界面微环境适于胎儿存活,从而维持母胎免疫耐受。

Soluble class Ib HLA-G（human leukocyte antigen-G） synthesized in the placenta are abundant in the pregnant uterus and circulate in maternal blood throughout pregnancy. It appears to be a key molecule present at the maternal-fetal interface at the implantation time. Our previous studies have demonstrated that the level of KIR2DL4, ILT-2, ILT-4 on placenta decidual tissue from RSA are much lower than that of normal fertile group, which remind us if the soluble HLA-G have any effects on the expressions of these NKRs （natural killer receptors）. To confirm our hypothesis, we cultured decidula immune cells, PBMC （peripheral blood mononuclear cells）, NK92 cell line with various concentrations of recombinant sHLA-G for 12 h, 24 h, 48 h, respectively. After extraction of total RNAs and synthesis of cDNAs, we determined the expression of the KIR2DL4, ILT-2, ILT-4 mRNA by real-time RT-PCR and FACS. It was found that the level of KIR2DL4, ILT-2, ILT-4 mRNA expression are up-regulated at different degrees in the presence of recombinant sHLA-G. This data show that sHLA-G, an immunomodulator molecule, can up-regulate the expression of NKR except for its known immunosuppressive function. The potential consequences of such up-regulation might therefore present advantages for HLA-G-expressing tissues that are potential targets for NK and cytotoxic T lymphocytes and be part of immune escape mechanisms.