Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Biomedical Sciences Program, University of California, San Francisco, San Francisco, CA 94143, USA.
Immunity. 2023 Mar 14;56(3):606-619.e7. doi: 10.1016/j.immuni.2023.01.005. Epub 2023 Feb 6.
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.
尽管正常情况下，当老鼠的卵巢停止分泌孕激素（黄体溶解）时，它们就会进入分娩期，但通过子宫内固有途径，也可以在这种动物身上引发分娩，其潜在机制类似于引发人类分娩的途径。然而，在这两种物种中，这些途径在很大程度上仍未得到明确界定。在这里，我们报告说，当通过内分泌手段操纵以规避黄体溶解时，先天 2 型免疫缺失的小鼠经历了严重的分娩延迟，从而迫使它们通过子宫内固有途径进入分娩期。我们发现，这些途径部分是由子宫间质成纤维细胞产生的警报素 IL-33 驱动的。我们还发现，子宫 2 型固有淋巴细胞和嗜酸性粒细胞在其中发挥了重要作用，在分娩开始前，这些细胞表现出依赖于 IL-33 的激活，并且在产前子宫中，这些细胞显示出证据表明其周转率升高。这些发现揭示了先天 2 型免疫在通过可能与人类分娩相关的级联反应控制分娩开始时间方面的作用。
