The role of RORγt at maternal-fetal interface during murine pregnancy.

Abstract

Innate lymphoid cells (ILCs, including NK cells) and their subsets are the most frequent lymphocytes at the maternal-fetal interface (decidua). Recent recognition of extensive ILC subset diversity at mucosal sites and the possible role they might play at different stages of pregnancy poses questions about their composition and lineage stability. Namely, RORγt-dependent ILC3s have been recognized as a key cellular mediator of tissue organization in the gut and secondary lymphoid organs, prompting examination of their distribution and role in decidua during pregnancy. We employed highly polychromatic flow cytometry with conventional and machine learning-aided analysis to map ILC subsets and dissected the role of canonical transcription factor RORγt using fate-mapping animals and RORγt-/- animals. We demonstrate a comprehensive immunome map of ILCs/NKs, revealing a dynamic interface even in the absence of antigenic or allogeneic challenge. Strikingly, we demonstrate plasticity of RORγt expression in decidual ILCs with across gestation. However, gross reproductive efficiency is not affected in RORγt-/- animals. These results indicated that RORγt+ ILCs are highly plastic at the maternal-fetal interface, but dispensable for normal pregnancy, revealing a novel mechanism of transcriptional immunoregulation in pregnancy.