Table_2_The immune checkpoint molecule, VTCN1/B7-H4, guides differentiation and suppresses proinflammatory responses and MHC class I expression in an embryonic stem cell-derived model of human trophoblast.xlsx

The placenta acts as a protective barrier to pathogens and other harmful substances present in the maternal circulation throughout pregnancy. Disruption of placental development can lead to complications of pregnancy such as preeclampsia, intrauterine growth retardation and preterm birth. In previous work, we have shown that expression of the immune checkpoint regulator, B7-H4/VTCN1, is increased upon differentiation of human embryonic stem cells (hESC) to an in vitro model of primitive trophoblast (TB), that VTCN1/B7-H4 is expressed in first trimester but not term human placenta and that primitive trophoblast may be uniquely susceptible to certain pathogens. Here we report on the role of VTCN1 in trophoblast lineage development and anti-viral responses and the effects of changes in these processes on major histocompatibility complex (MHC) class I expression and peripheral NK cell phenotypes.

胎盘在整个妊娠周期中可作为保护性屏障，阻隔母体循环内的病原体与其他有害物质。胎盘发育异常可诱发子痫前期、宫内生长受限及早产等多种妊娠并发症。既往研究中，本团队已证实：人类胚胎干细胞（human embryonic stem cells，hESC）向体外原始滋养层细胞（trophoblast，TB）模型分化时，免疫检查点调节因子B7-H4/VTCN1的表达水平显著上调；VTCN1/B7-H4仅在妊娠第一孕期的人胎盘中表达，足月胎盘则无该因子表达；且原始滋养层细胞可能对特定病原体具有独特易感性。本研究报道了VTCN1在滋养层谱系发育与抗病毒应答中的调控作用，以及上述过程的改变对主要组织相容性复合体（major histocompatibility complex，MHC）I类分子表达及外周NK细胞表型的影响。