Circumvention 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 labor onset, and eosinophils, which displayed evidence of elevated turnover in the prepartum uterus. These findings reveal a role for innate type 2 immunity in controlling the timing of labor onset through a cascade potentially relevant to human parturition. Copyright © 2023 Elsevier Inc. All rights reserved.

Citation

Johan Siewiera, Tara I McIntyre, Kelly M Cautivo, Karim Mahiddine, Damon Rideaux, Ari B Molofsky, Adrian Erlebacher. Circumvention of luteolysis reveals parturition pathways in mice dependent upon innate type 2 immunity. Immunity. 2023 Mar 14;56(3):606-619.e7

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PMID: 36750100

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