The establishment of maternal immunotolerance is essential for the survival of allogeneic fetuses. In the Proceedings of the National Academy of Science, Nadkarni et al. report a role for neutrophils exposed to maternal hormones that help establish a 'tolerant' environment within the developing placenta. These 'tolerogenic' neutrophils upregulate expression of the transcription factor Foxo1 and annexin-A1 and release apoptotic bodies that then promote the generation of fetal-antigen-specific regulatory T cells that express IL-10 and IL-17. IL-17 enhances pro-angiogenic activities necessary for placental growth and decidualization. Depletion of neutrophils in pregnant mice leads to defective placental development and decreases the number of viable fetuses. Similarly, neutrophils from women with pre-eclampsia fail to induce regulatory T cells and express less Foxo1 than do neutrophils from healthy expectant mothers. These findings indicate a role for the neutrophil-mediated transfer of Foxo1 to CD4+ T cells to induce Foxp3 expression within the uterine environment.

Proc. Natl. Acad. Sci. USA (12 December 2016) http://dx.doi.org/10.1073/pnas.1611944114