Regulation of pregnancy maintenance and fetal survival in mice by CD27low mature NK cells
- 345 Downloads
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 CD27lowDX5+CD3neg, 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 CD27low 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 CD27low NK cells are also present in human decidua, the CD27low NK subset may provide a tool to foster translational research in reproduction, aiming to improve pregnancy outcome in humans.
KeywordsNK subsets CD27 Reproduction Alymphoid mice Cytotoxicity
We thank Evelin Hagen for her assistance in generating some of the data. We also thank M. Ito (Central Institute for Experimental Animals, Kawasaki, Japan) for providing us with initial breeding pairs of Rag2−/−/γc−/− mice. This work was supported by research grants provided to P.C.A. by the German Research Foundation and the Excellence Initiative of the Hamburg Foundation for Research.
Conflict of interest disclosure
The authors declare no competing financial interests.
- 24.Carlino C, Stabile H, Morrone S, Bulla R, Soriani A, Agostinis C, Bossi F, Mocci C, Sarazani F, Tedesco F et al (2008) Recruitment of circulating NK cells through decidual tissues: a possible mechanism controlling NK cell accumulation in the uterus during early pregnancy. Blood 111:3108–3115PubMedCrossRefGoogle Scholar
- 25.Mazurier F, Fontanellas A, Salesse S, Taine L, Landriau S, Moreau-Gaudry F, Reiffers J, Peault B, Di Santo JP, de Verneuil H (1999) A novel immunodeficient mouse model—RAG2 × common cytokine receptor gamma chain double mutants—requiring exogenous cytokine administration for human hematopoietic stem cell engraftment. J Interferon Cytokine Res 19:533–541PubMedCrossRefGoogle Scholar