Repository logo

Disrupted PI3K p110δ Signaling Dysregulates Maternal Immune Cells and Increases Fetal Mortality In Mice.

Change log


Balmas, Elisa 
Hawkes, Delia A 


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 p110δ, a key intracellular signaling molecule in leukocytes, we show that p110δ regulates macrophage dynamics and NK-cell-mediated arterial remodeling. The uterus of dams with inactive p110δ had decreased IFN-γ 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.



Animals, Class I Phosphatidylinositol 3-Kinases, Cytokines, Disease Models, Animal, Female, Fetal Death, Fetal Growth Retardation, Gene Silencing, Interferon-gamma, Killer Cells, Natural, Macrophages, Mice, Phosphatidylinositol 3-Kinases, Pregnancy, Signal Transduction, Uterus

Journal Title

Cell Rep

Conference Name

Journal ISSN


Volume Title



Elsevier BV
Wellcome Trust (094073/Z/10/Z)
We would like to thank Klaus Okkenhaug for the provision of the δᴰ⁹¹⁰ᴬ strain, Anne-Katrien Stark for making breeding records available, all members of the Colucci lab for helpful discussions and the staff of the NIHR Cambridge BRC Cell Phenotyping Hub for their support. This work was supported by the Cambridge NIHR BRC Cell Phenotyping Hub and by grants from The Wellcome Trust [094073/Z/10/Z] and the Centre for Trophoblast Research.