Research ArticleImmunology

Tim-3 signaling in peripheral NK cells promotes maternal-fetal immune tolerance and alleviates pregnancy loss

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Sci. Signal.  26 Sep 2017:
Vol. 10, Issue 498, eaah4323
DOI: 10.1126/scisignal.aah4323

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Mediating maternal-fetal tolerance

Many cases of recurrent miscarriage are due to a breakdown in immune tolerance between the mother and the fetus. Determining the underlying mechanism may aid in the identification of biomarkers for recurrent miscarriage and suggest possible therapies. Li et al. found that the abundance of the type I membrane receptor Tim-3 was increased on the surface of peripheral natural killer (pNK) cells in the first trimester of pregnancy. These cells produced anti-inflammatory cytokines and induced the generation of immunosuppressive cells. In contrast to pNK cells from donors with normal pregnancies, those from recurrent miscarriage patients had decreased Tim-3 abundance and were defective in immunosuppression. Experiments with abortion-prone mice showed that Tim-3+ pNK cells, but not Tim-3 pNK cells, protected against fetal loss, suggesting that Tim-3+ pNK cells promote maternal-fetal immune tolerance.