ADAR1 as a Placental Innate Immune Rheostat Sustaining the Homeostatic Balance of Intrinsic Interferon Response at the Maternal-Fetal Interface.

ABSTRACT: The mechanisms that balance a robust intrinsic antiviral defense at the maternal-fetal interface with fetal development remain elusive. Here, it is delineated that ADAR1, an adenosine-to-inosine (A-to-I) editor, fine-tunes intrinsic interferon (IFN)-mediated integrates stress response (ISR) in the mouse placenta, thereby orchestrating embryonic development and antiviral defense. Placental Adar1 deletion (Adar1^PKO) trigger spatially resolved overwhelming IFN responses, which impair the differentiation of IFN hyper-responsive junctional zone (JZ) progenitors and functions of the placental JZ, ultimately causing embryonic death. Mechanistically, the Adar1^PKO placental IFN hyper-response is positively amplified by the accumulated immunogenic dsRNAs from the 3'UTR of inter

SUBMITTER: Chen X 

PROVIDER: S-EPMC12622419 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature