biostudies-literatureSiewiera JNational Institute of Allergy and Infectious DiseasesNIAID NIH HHSNIH606-619.e7https://www.ebi.ac.uk/biostudies/studies/S-EPMC10023352biostudies-literatureUnknown56(3)Although mice normally enter labor when their ovaries stop producing progesterone (luteolysis), parturition can also be triggered in this species through uterus-intrinsic pathways potentially analogous to the ones that trigger parturition in humans. Such pathways, however, remain largely undefined in both species. Here, we report that mice deficient in innate type 2 immunity experienced profound parturition delays when manipulated endocrinologically to circumvent luteolysis, thus obliging them to enter labor through uterus-intrinsic pathways. We found that these pathways were in part driven by the alarmin IL-33 produced by uterine interstitial fibroblasts. We also implicated important roles for uterine group 2 innate lymphoid cells, which demonstrated IL-33-dependent activation prior to laImmunityCircumvention of luteolysis reveals parturition pathways in mice dependent upon innate type 2 immunity.PMC10023352R01 AI150191R01 AI106745R01AI150191T32 AI007334Siewiera JMahiddine KMcIntyre TIErlebacher AMolofsky ABCautivo KMRideaux DfalseCircumvention of luteolysis reveals parturition pathways in mice dependent upon innate type 2 immunity.Although mice normally enter labor when their ovaries stop producing progesterone (luteolysis), parturition can also be triggered in this species through uterus-intrinsic pathways potentially analogous to the ones that trigger parturition in humans. Such pathways, however, remain largely undefined in both species. Here, we report that mice deficient in innate type 2 immunity experienced profound parturition delays when manipulated endocrinologically to circumvent luteolysis, thus obliging them to enter labor through uterus-intrinsic pathways. We found that these pathways were in part driven by the alarmin IL-33 produced by uterine interstitial fibroblasts. We also implicated important roles for uterine group 2 innate lymphoid cells, which demonstrated IL-33-dependent activation prior to la2023-01-01T00:00:00Z2023 Mar2026-06-01T08:09:18.771Z2024-10-16T07:30:36.149ZS-EPMC100233523675010010.1016/j.immuni.2023.01.005