Uterine NK cells: active regulators at the maternal-fetal interface
Ashley Moffett, Francesco Colucci
Ashley Moffett, Francesco Colucci
Published May 1, 2014
Citation Information: J Clin Invest. 2014;124(5):1872-1879. https://doi.org/10.1172/JCI68107.
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Uterine NK cells: active regulators at the maternal-fetal interface

Abstract

Pregnancy presents an immunological conundrum because two genetically different individuals coexist. The maternal lymphocytes at the uterine maternal-fetal interface that can recognize mismatched placental cells are T cells and abundant distinctive uterine NK (uNK) cells. Multiple mechanisms exist that avoid damaging T cell responses to the fetus, whereas activation of uNK cells is probably physiological. Indeed, genetic epidemiological data suggest that the variability of NK cell receptors and their MHC ligands define pregnancy success; however, exactly how uNK cells function in normal and pathological pregnancy is still unclear, and any therapies aimed at suppressing NK cells must be viewed with caution. Allorecognition of fetal placental cells by uNK cells is emerging as the key maternal-fetal immune mechanism that regulates placentation.

Authors

Ashley Moffett, Francesco Colucci

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Figure 2

NK cell education and recognition of allogeneic paternal MHC molecules on trophoblast cells.

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NK cell education and recognition of allogeneic paternal MHC molecules o...
Individuals inherit one KIR haplotype on chromosome 19 from each parent. Each haplotype contains 7–15 genes (only a few are depicted here for clarity). During NK cell differentiation, KIR genes are expressed in developing NK cells. Each NK cell expresses 0–5 KIRs. Some of the KIRs bind to self MHC molecules and educate NK cells to be tolerant of self and also to react to the absence of self. Allogeneic, paternal MHC molecules on the trophoblast cell can interact with some KIRs on the uNK cell; however, it is not known whether this new interaction educates uNK cells or if the uNK cells recognize the paternal, allogeneic MHC molecule as foreign, generating an alloresponse.