Human Amnion Epithelial Cells Impair T Cell Proliferation: The Role of HLA-G and HLA-E Molecules.

Human Amnion Epithelial Cells Impair T Cell Proliferation: The Role of HLA-G and HLA-E Molecules.
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人羊膜上皮细胞会损害T细胞增殖:HLA-G和HLA-E分子的作用。

DOI:
10.3390/cells9092123
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发表时间:
2020-09-19
期刊:
影响因子:
6
通讯作者:
Gramignoli R
Gramignoli R
中科院分区:
生物学2区
文献类型:
--
作者:
Morandi F;Marimpietri D;Görgens A;Gallo A;Srinivasan RC;El-Andaloussi S;Gramignoli R

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人羊膜上皮细胞(hAEC)的免疫豁免状态特征最近在异种移植的背景下得到了强调。然而,迄今为止,涉及此类监管功能的机制仅得到部分阐明。在这里,我们分析了从足月胎盘获得的分离 hAEC 中 HLA-Ib 分子的表达。此外,我们询问这些分子是否参与 hAEC 的免疫调节功能。人羊膜来源的细胞表面 HLA-G 和 HLA-F 表达水平很高,而通常表达的 HLA-E 分子在新鲜分离的细胞中表达水平很低或为零。 HLA-Ib分子可以以膜结合和可溶形式表达,并且在分析的所有hAEC批次中,当hAEC维持在培养物中时,我们测量到高水平的sHLA-G和sHLA-E,并且这种释放是时间依赖性的。此外,HLA-G 存在于 hAEC 释放的细胞外囊泡 (EV) 中。如先前报道,hAEC 在不同的 hAEC:T 细胞比例下在体外抑制 T 细胞增殖。此外,用抗HLA-G、抗HLA-E和抗β2微球蛋白预处理hAEC可部分逆转T细胞增殖的抑制,因此表明HLA-G和-E分子参与hAEC介导的T细胞增殖抑制。最后,源自 hAEC 的大尺寸 EV (lsEV) 或小尺寸 EV (ssEV) 显着调节 T 细胞增殖。总之,我们在此描述了 hAEC 免疫调节功能的潜在机制之一,与 HLA-Ib 分子的表达和释放有关。
The immunoprivilege status characteristic of human amnion epithelial cells (hAECs) has been recently highlighted in the context of xenogenic transplantation. However, the mechanism(s) involved in such regulatory functions have been so far only partially been clarified. Here, we have analyzed the expression of HLA-Ib molecules in isolated hAEC obtained from full term placentae. Moreover, we asked whether these molecules are involved in the immunoregulatory functions of hAEC. Human amnion-derived cells expressed surface HLA-G and HLA-F at high levels, whereas the commonly expressed HLA-E molecule has been measured at a very low level or null on freshly isolated cells. HLA-Ib molecules can be expressed as membrane-bound and soluble forms, and in all hAEC batches analyzed we measured high levels of sHLA-G and sHLA-E when hAEC were maintained in culture, and such a release was time-dependent. Moreover, HLA-G was present in extracellular vesicles (EVs) released by hAEC. hAEC suppressed T cell proliferation in vitro at different hAEC:T cell ratios, as previously reported. Moreover, inhibition of T cell proliferation was partially reverted by pretreating hAEC with anti-HLA-G, anti-HLA-E and anti-β2 microglobulin, thus suggesting that HLA-G and -E molecules are involved in hAEC-mediated suppression of T cell proliferation. Finally, either large-size EV (lsEV) or small-size EV (ssEV) derived from hAEC significantly modulated T-cell proliferation. In conclusion, we have here characterized one of the mechanism(s) underlying immunomodulatory functions of hAEC, related to the expression and release of HLA-Ib molecules.
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