Oxygen regulates ILC3 antigen presentation potential and pregnancy-related hormone actions

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.