Natural killer (NK) cells have a protective role in establishing and maintaining maternal tolerance to a developing fetus. In Science Signaling, Li et al. show that peripheral NK cells upregulate their expression of the immunoinhibitory molecule Tim-3 during the first trimester of pregnancy and thereby promote maternal–fetal tolerance via interaction with the Tim-3 ligand galectin-9. Tim-3+ NK cells express anti-inflammatory cytokines and are less cytotoxic than Tim-3− NK cells. NK cells from women who have experienced recurrent miscarriages have lower expression of Tim-3 protein and are more cytotoxic than NK cells obtained during a normal pregnancy. Corresponding differences at the chromatin level and in gene expression are also seen in Tim-3+ and Tim-3− NK cells. Tim-3+ NK cells also contribute to an increased frequency of induced regulatory T cells dependent on the cytokine TGF-β1, which suggests another mode by which NK cells contribute to maternal–fetal tolerance.

Sci. Signal. 10, eaa4323 (26 September 2017)