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. 2012 Sep;90(9):1047-57.
doi: 10.1007/s00109-012-0872-5. Epub 2012 Feb 23.

Regulation of pregnancy maintenance and fetal survival in mice by CD27(low) mature NK cells

Khalil Karimi  1 , María Emilia Solano, Ali A Ashkar, Huang Ho, Eva-Maria Steidle, Karen-Anne McVey Neufeld, Kurt Hecher, John Bienenstock, Petra Clara Arck
Affiliations

Regulation of pregnancy maintenance and fetal survival in mice by CD27(low) mature NK cells

Khalil Karimi et al. J Mol Med (Berl). 2012 Sep.

Erratum in

  • J Mol Med (Berl). 2013 Jul;91(7):903-4

Abstract

Uterine natural killer (NK) cells are pivotal for successful mammalian reproduction. However, insights on functionally distinct subpopulations of uterine NK cells are largely elusive. Furthermore, translation of findings from murine into human pregnancy has been overshadowed by the limited number of mutual phenotypic NK cell markers. We here provide evidence that a subset of murine mature NK (mNK) cells present at the feto-maternal interface, identified as CD27(low)DX5(+)CD3(neg), is pivotal in maintaining pregnancy. This mNK subset has low cytotoxic capacity, produces higher amounts of interferon (IFN)-γ, and expresses functional homologs of human NK cell immunoglobulin-like receptors. We further show that bone marrow-derived CD27(low) mNK cells are selectively recruited to the uterus and ameliorate the rate of fetal loss when adoptively transferred into alymphoid RAG2(-/-)/γc(-/-) mice. Additionally, expression of CD27 is down-modulated on mNK cells upon migration to the uterus. Hence, we propose the existence of a regulatory mNK cell subset, which is licensed toward successful pregnancy maintenance at the fetomaternal interface in mice. As CD27(low) NK cells are also present in human decidua, the CD27(low) NK subset may provide a tool to foster translational research in reproduction, aiming to improve pregnancy outcome in humans.

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