Gab3 mutation prevents NK cells formation leading to placenta accreta

Gab3 mutation prevents NK cells formation leading to placenta accreta

Sliz et al discovered a remarkable association between risk for placenta accreta in pregnant women with a gene mutation that prevents the healthy formation of “natural killer” cells (NK). The researchers found that the mice which carried a mutation in a protein called Grb2-associated binding protein 3 (Gab3) was responsible for preventing normal NK cell expansion in the uterus. Loss of Gab3 resulted in impaired IL-2 and IL-15–induced NK cell priming and expansion due to a selective impairment in MAPK signalling. Gab3-deficient mice exhibited impaired uterine NK cell expansion associated with abnormal spiral artery remodelling and increased trophoblast invasion in the decidua basalis. This coincided with stillbirth, retained placenta, maternal haemorrhage, and undelivered fetoplacental units at term. The findings unveiled the important role of Gab3 during pregnancy which could lead to a reliable biomarker to detect the condition that may help to proactively treat accreta.

Source: Science Immunology 02 Aug 2019: Vol. 4, Issue 38, eaav3866 DOI: 10.1126/sciimmunol.aav3866 https://immunology.sciencemag.org/content/4/38/eaav3866

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