| First Author | Kieckbusch J | Year | 2015 |
| Journal | Cell Rep | Volume | 13 |
| Issue | 12 | Pages | 2817-28 |
| PubMed ID | 26711346 | Mgi Jnum | J:265969 |
| Mgi Id | MGI:6207137 | Doi | 10.1016/j.celrep.2015.11.050 |
| Citation | Kieckbusch J, et al. (2015) Disrupted PI3K p110delta Signaling Dysregulates Maternal Immune Cells and Increases Fetal Mortality In Mice. Cell Rep 13(12):2817-28 |
| abstractText | Maternal immune cells are an integral part of reproduction, but how they might cause pregnancy complications remains elusive. Macrophages and their dual function in inflammation and tissue repair are thought to play key yet undefined roles. Altered perinatal growth underpins adult morbidity, and natural killer (NK) cells may sustain fetal growth by establishing the placental blood supply. Using a mouse model of genetic inactivation of PI3K p110delta, a key intracellular signaling molecule in leukocytes, we show that p110delta regulates macrophage dynamics and NK-cell-mediated arterial remodeling. The uterus of dams with inactive p110delta had decreased IFN-gamma and MHC class II(low) macrophages but enhanced IL-6. Poor vascular remodeling and a pro-inflammatory uterine milieu resulted in fetal death or growth retardation. Our results provide one mechanism that explains how imbalanced adaptations of maternal innate immune cells to gestation affect offspring well-being with consequence perinatally and possibly into adulthood. |
