Strategically located in mucosal barriers, innate lymphoid cells (ILCs) are relevant in local containment and tolerance of commensal microflora. ILCs have been recently described at the fetomaternal interface, where the development of a semi-allogeneic fetus can only succeed in a well-controlled immune environment. We postulate that ILCs adapt their antigen presentation capacity to protect pregnancy from excessive immune responses. Human ILCs were studied in deciduae of term pregnancies, peripheral blood and in in vitro generated ILCs. Fresh isolated lymphocytes or cells treated with pregnancy-related factors were investigated. The fetal antigen rejection-based CBA/J × DBA/2J mouse model (poor outcome pregnant mice; POPM) was used to characterize ILC antigen presentation potential in normal and immunologically disturbed pregnancies. ILC antigen presentation potential was characterized by flow cytometry and qPCR. We discovered that the distribution of ILC subsets changed during both, human and murine pregnancy. Moreover, the pregnancy was accompanied by reduced MHCII expression in splenic ILCs during normal pregnancy (CBA/J × BALB/c; good outcome pregnant mice; GOPM) but increased in splenic and intestinal ILCs of CBA/J × DBA/2J mice. In vitro, splenic ILCs from pregnant mice increased MHCII expression after stimulation with IL-1β, IL-23. In contrast, uterine ILCs displayed lower MHCII expression, which remained unchanged after stimulation. Finally, pregnancy-related factors and hormones present in the uterine environment reduced antigen presentation potential of human ILCs in vitro. Together, these data indicate that during pregnancy, peripheral and especially uterine ILCs adapt their antigen presenting potential to maintain a level of tolerance and support pregnancy.

中文翻译：

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怀孕期间激素控制的 ILC 抗原呈递潜力降低

先天淋巴细胞 (ILC) 战略性地位于粘膜屏障中，与共生微生物群落的局部遏制和耐受性相关。最近在胎母界面描述了 ILC，其中半同种异体胎儿的发育只能在良好控制的免疫环境中成功。我们假设 ILC 调整其抗原呈递能力以保护怀孕免受过度免疫反应的影响。在足月妊娠的蜕膜、外周血和体外产生的 ILC 中研究了人类 ILC。研究了新鲜分离的淋巴细胞或用妊娠相关因子处理的细胞。基于胎儿抗原排斥的 CBA/J × DBA/2J 小鼠模型（不良结果妊娠小鼠；POPM）用于表征正常和免疫紊乱妊娠中的 ILC 抗原呈递潜力。ILC 抗原呈递潜力通过流式细胞术和 qPCR 进行表征。我们发现 ILC 子集的分布在人类和小鼠怀孕期间都发生了变化。此外，妊娠伴随着正常妊娠期间脾脏 ILC 中 MHCII 的表达降低（CBA/J × BALB/c；良好结果妊娠小鼠；GOPM），但在 CBA/J × DBA/2J 小鼠的脾脏和肠道 ILC 中表达增加。在体外，来自怀孕小鼠的脾脏 ILC 在用 IL-1β、IL-23 刺激后增加了 MHCII 表达。相比之下，子宫 ILC 显示出较低的 MHCII 表达，刺激后保持不变。最后，子宫环境中存在的妊娠相关因素和激素降低了体外人 ILC 的抗原呈递潜力。总之，这些数据表明，在怀孕期间，