Oxygen regulates ILC3 antigen presentation potential and pregnancy-related hormone actions.
Oxygen regulates ILC3 antigen presentation potential and pregnancy-related hormone actions.
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DOI：
10.1186/s12958-022-00979-2
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发表时间：
2022-07-29
影响因子：
4.4
通讯作者：
Muzzio, Damian Oscar
中科院分区：
文献类型：
--
作者：
Einenkel, Rebekka;Ehrhardt, Jens;Zygmunt, Marek;Muzzio, Damian Oscar
早期妊娠以胎盘形成和胚胎发生为标志，这发生在生理低氧浓度下。这种氧气条件对胎盘形成、滋养层功能、血管形成和免疫功能的许多方面都至关重要。最近，一个新的家族的先天淋巴样细胞已被发现在母胎界面表达。其中，3型先天淋巴样细胞（ILC 3）是MHC-II背景下重要的抗原呈递细胞。在妊娠期间，ILC 3上MHC-II的表达减少。我们测试了低氧浓度降低ILC 3呈递促进胎儿耐受的抗原的潜力的假设。使用体外方法，在存在或不存在妊娠相关激素hCG和TGF-β1的情况下，在不同O2浓度下孵育由脐带血干细胞前体产生的NCR+ ILC 3。通过流式细胞术评估MHC-II、辅助分子和活化标志物的表达。我们观察到，与21% O2相比，1% O2降低了MHC-II分子HLA-DR的表达，并调节了hCG和TGF-β1的相对作用。我们的数据表明，低氧浓度降低了NCR+ ILC 3的抗原呈递潜力，并表明它可能在妊娠的前三个月促进胎儿耐受。在线版本包含补充材料，可通过10.1186/s12958-022-00979-2获得。
Early pregnancy is marked by placentation and embryogenesis, which take place under physiological low oxygen concentrations. This oxygen condition is crucial for many aspects of placentation, trophoblast function, vascularization and immune function. Recently, a new family of innate lymphoid cells has been found to be expressed at the fetomaternal interface. Among these, type 3 innate lymphoid cells (ILC3) are important antigen presenting cells in the context of MHC-II. The expression of MHC-II on ILC3s during pregnancy is reduced. We tested the hypothesis that low oxygen concentrations reduce the potential of ILC3s to present antigens promoting fetal tolerance. Using an in vitro approach, NCR+ ILC3s generated from cord blood stem cell precursors were incubated under different O2 concentrations in the presence or absence of the pregnancy-related hormones hCG and TGF-β1. The expression of MHC-II, accessory molecules and an activation marker were assessed by flow cytometry. We observed that 1% O2 reduced the expression of the MHC-II molecule HLA-DR as compared to 21% O2 and modulated the relative effects of hCG and TGF-β1. Our data indicate that low oxygen concentrations reduce the antigen presentation potential of NCR+ ILC3s and suggest that it may promote fetal tolerance during the first trimester of pregnancy. The online version contains supplementary material available at 10.1186/s12958-022-00979-2.
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DOI：
10.4049/jimmunol.1202582
发表时间：
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期刊：
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