Research ArticleNK CELLS

Gab3 is required for IL-2– and IL-15–induced NK cell expansion and limits trophoblast invasion during pregnancy

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Science Immunology  02 Aug 2019:
Vol. 4, Issue 38, eaav3866
DOI: 10.1126/sciimmunol.aav3866

Gab3 adaptor prevents NK cell dysfunction

Natural killer (NK) cells are innate effector cells that help defend mammals from viral infections and cancer while acting locally in the uterus to support successful pregnancy outcomes. Sliz et al. used a chemical mutagenesis screen in mice to identify Gab3 as a scaffolding protein required for NK cell priming and peripheral expansion in response to cytokines. Gab3 mutant mice exhibited defects in their ability to control tumors and successfully complete pregnancies because of impaired NK cell function. This study identifies an adaptor protein required to achieve full NK cell function and enhances our understanding of how subtle uterine NK cell perturbations can contribute to the demise of pregnancies. See related Focus by Colucci.

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