Pianta Stefano, Magatti Marta, Vertua Elsa, Bonassi Signoroni Patrizia, Muradore Ivan, Nuzzo Anna Maria, Rolfo Alessandro, Silini Antonietta, Quaglia Federico, Todros Tullia, Parolini Ornella
Centro di Ricerca E. Menni, Fondazione Poliambulanza-Istituto Ospedaliero, Brescia, Italy.
Doctoral School of Translational and Molecular Medicine, University of Milan, Milan, Italy.
J Cell Mol Med. 2016 Jan;20(1):157-69. doi: 10.1111/jcmm.12715. Epub 2015 Oct 30.
Pre-eclampsia (PE) is one of the most severe syndromes in human pregnancy, and the underlying mechanisms of PE have yet to be determined. Pre-eclampsia is characterized by the alteration of the immune system's activation status, an increase in inflammatory Th1/Th17/APC cells, and a decrease in Th2/Treg subsets/cytokines. Moreover, inflammatory infiltrates have been detected in the amniotic membranes of pre-eclamptic placentae, and to this date limited data are available regarding the role of amniotic membrane cells in PE. Interestingly, we and others have previously shown that human amniotic mesenchymal stromal cells (hAMSC) possess anti-inflammatory properties towards almost all immune cells described to be altered in PE. In this study we investigated whether the immunomodulatory properties of hAMSC were altered in PE. We performed a comprehensive study of cell phenotype and investigated the in vitro immunomodulatory properties of hAMSC isolated from pre-eclamptic pregnancies (PE-hAMSC), comparing them to hAMSC from normal pregnancies (N-hAMSC). We demonstrate that PE-hAMSC inhibit CD4/CD8 T-cell proliferation, suppress Th1/Th2/Th17 polarization, induce Treg and block dendritic cells and M1 differentiation switching them to M2 cells. Notably, PE-hAMSC generated a more prominent induction of Treg and higher suppression of interferon-γ when compared to N-hAMSC, and this was associated with higher transforming growth factor-β1 secretion and PD-L2/PD-L1 expression in PE-hAMSC. In conclusion, for the first time we demonstrate that there is no intrinsic impairment of the immunomodulatory features of PE-hAMSC. Our results suggest that amniotic mesenchymal stromal cells do not contribute to the disease, but conversely, could participate in offsetting the inflammatory environment which characterizes PE.
子痫前期（PE）是人类妊娠中最严重的综合征之一，其潜在机制尚未明确。子痫前期的特征是免疫系统激活状态改变、促炎的Th1/Th17/抗原呈递细胞（APC）增加以及Th2/Treg亚群/细胞因子减少。此外，在子痫前期胎盘的羊膜中已检测到炎症浸润，迄今为止，关于羊膜细胞在子痫前期中的作用的数据有限。有趣的是，我们和其他人之前已经表明，人羊膜间充质基质细胞（hAMSC）对几乎所有在子痫前期中被描述为发生改变的免疫细胞都具有抗炎特性。在本研究中，我们调查了子痫前期中hAMSC的免疫调节特性是否发生改变。我们对细胞表型进行了全面研究，并研究了从子痫前期妊娠中分离的hAMSC（PE-hAMSC）的体外免疫调节特性，并将其与正常妊娠的hAMSC（N-hAMSC）进行比较。我们证明，PE-hAMSC抑制CD4/CD8 T细胞增殖，抑制Th1/Th2/Th17极化，诱导调节性T细胞（Treg）并阻断树突状细胞和M1分化，将它们转变为M2细胞。值得注意的是，与N-hAMSC相比，PE-hAMSC对Treg的诱导作用更显著，对干扰素-γ的抑制作用更强，这与PE-hAMSC中更高的转化生长因子-β1分泌和PD-L2/PD-L1表达有关。总之，我们首次证明PE-hAMSC的免疫调节特征没有内在损伤。我们的结果表明，羊膜间充质基质细胞不会导致该疾病，相反，可能参与抵消子痫前期所特有的炎症环境。
