Interaction between uterine natural killer cells and extravillous trophoblast cells: effect on cytokine and angiogenic growth factor production

Lash, GE; Naruse, Katsuhiko; Robson, A. J.; Innes, Barbara A.; Searle, Roger F.; Robson, S. C.; Bulmer, Judith N.

doi:10.1016/j.jri.2011.06.017

Cited by 7 publications

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“…The observation that CM derived from uNK/EVT cocultures is less bioactive than CM derived from uNK cell cultures alone highlights the importance of spatio‐temporal regulation of different cell types during sequential remodeling events and might explain why decidual leukocytes initiate vascular disruption before the arrival of EVT cells (10). We have reported that CM from uNK cell/EVT cocultures contains reduced levels of Ang‐1 and VEGF‐C compared with expected levels based on secretion by cultures of uNK cells or EVT cells alone (26). This result suggests that there is a negative feedback loop between uNK and EVT cells that limits the local secretion of angiogenic growth factors and perhaps limits the rate of the SpA remodeling process.…”

Section: Discussionmentioning

confidence: 96%

“…EVT cells were isolated from first‐trimester placenta as described previously (25, 26), and 1 × 10 6 cells/ml were cultured for 24 h in a 24‐well plate in DMEM‐Ham's F12 supplemented with 10% FBS, 2 mM glutamine, 100 U/ml penicillin, and 0.1 mg/ml streptomycin (all from Sigma‐Aldrich; DMEM‐Ham's F12 complete medium) on growth factor‐reduced Matrigel (BD Biosciences, Franklin Lakes, NJ); CM (EVT‐CM) was then harvested. Cell purity was tested by immunostaining for HLA‐G and cytokeratin 7 as described previously (25), and viability was assessed by exclusion of trypan blue; both viability and purity were consistently >95%.…”

Section: Methodsmentioning

confidence: 99%

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Uterine natural killer cells initiate spiral artery remodeling in human pregnancy

et al. 2012

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Uterine spiral artery remodeling is required for successful human pregnancy; impaired remodeling is associated with pregnancy complications, including late miscarriage, preeclampsia, and fetal growth restriction. The molecular triggers of remodeling are not known, but it is now clear that there are "trophoblast-independent" and "trophoblast-dependent" stages. Uterine natural killer (uNK) cells are abundant in decidualized endometrium in early pregnancy; they surround spiral arteries and secrete a range of angiogenic growth factors. We hypothesized that uNK cells mediate the initial stages of spiral artery remodeling. uNK cells and extravillous trophoblast (EVT) cells were isolated from early pregnancy decidua and placenta. Chorionic plate arteries from full-term placentas and spiral arteries from nonpregnant myometrium were cultured with angiogenic growth factors or conditioned medium (CM) from uNK cells or EVT or uNK cell/EVT cocultures. In both vessel models, uNK cell CM induced disruption of vascular smooth muscle cells (VSMCs) and breakdown of extracellular matrix components. Angiopoietin (Ang)-1, Ang-2, interferon-γ, and VEGF-C also disrupted VSMC integrity with an Ang-2 inhibitor abrogating the effect of uNK cell CM. These results provide compelling evidence that uNK cells contribute to the early stages of spiral artery remodeling; failure of this process could contribute to pregnancy pathology.

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Section: Discussionmentioning

confidence: 96%

Section: Methodsmentioning

confidence: 99%

Uterine natural killer cells initiate spiral artery remodeling in human pregnancy

et al. 2012

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“…[14][15][16] Recent findings, both in humans and mice, have shown that uterine NK cells are involved in endometrial remodeling, spiral artery modifications and placentation. [17][18][19][20][21] Although a large body of information on uterine NK cell function comes from data in mice, our knowledge regarding the presence and the phenotype of murine NK cells in decidua and uterus during early pregnancy (first week) is still incomplete. Another important question concerns their origin: they can be generated in situ from precursors or recruited from the periphery into decidua and uterus, where the microenvironment can modulate their phenotypic and functional characteristics.…”

Section: Introductionmentioning

confidence: 99%

In vivo generation of decidual natural killer cells from resident hematopoietic progenitors

et al. 2013

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© F e r r a t a S t o r t i F o u n d a t i o nproperties of mature NK cells. Various markers allow the identification of different stages of NK cell maturation. The first to appear are NKG2D and NK1.1, followed by NKp46, CD94/NKG2A/C/E, CD27, DX5, Ly49 receptors and CD11b. 28,36 39 A recent report suggested that mouse uNK cells are heterogeneous and considering only DBA + uNK cells could bias information on the uNK cell population. 40 Since studies in humans clearly indicated that NK cells represent the most frequent lymphoid cell population during early pregnancy (first trimester), playing a fundamental role in the establishment and maintenance of pregnancy, it would be important to gain more information in mice. 12,18,41,42 In the present study, for the first time, murine NK cells were analyzed separately in decidua and uterus. We found that high proportions of immature NK cells are present both in decidua and uterus during the first week of pregnancy. In addition, we identified NK-committed hematopoietic precursors (Lin -CD122 + ) in decidua and uterus of pregnant mice. Transfer experiments of peripheral EGFP + -NK cells indicated that these cells are not recruited mainly into decidua and uterus, thus do not contribute to the accumulation of dNK and uNK cells during early pregnancy. In contrast, EGFP + -NKP transferred into pregnant mice rapidly migrated into decidua and uterus where they underwent proliferation and differentiation towards mature NK cells. Immature dNK and uNK display phenotypic and functional features similar to those previously described in humans. These data provide important information regarding the biology of NK cells in pregnancy, and identify novel tissues (decidua and uterus) able to sustain peripheral NK cell differentiation in vivo. MethodsC57BL/6 and RAG-2 -/-mice were purchased from Charles River. Transplant donors were EGFP+ transgenic mice ((C57BL/6-Tg(ACTB-EGFP)1 Osb/J mice 5 (GFP-Tg)). Cells derived from spleen, decidua, uterus and BM were incubated with different mAbs and run on a flow cytometer. EGFP + NK cells and NKP were injected intravenously into unirradiated wild-type syngeneic mice at gestational day (gd) 0,5. The presence and the phenotype of the transferred EGFP + cells were analyzed in the different tissues at gd 3,5-5,5-7,5 by flow cytometry. Mice were given one i.p. injection of 1 mg of 5-bromo-2'-deoxyuridine (BrdU). After 18 h, mice were sacrificed and organs were analyzed. Frozen sections of pregnant uteri were stained with anti-NKp46 (R & D Systems, Minneapolis, MN, USA) and anti-Ki-67 (Abcam, Cambridge, UK) followed by Alexa 594 chicken anti-goat and Alexa 488 goat anti-rabbit (Life Technologies, CA, USA). The nuclei were counterstained with DAPI. Cells derived from decidua, uterus and spleen of pregnant mice at gd 5.5 were stimulated during 4 h-culture with the different antibodies, or with YAC-1 mouse lymphoma cells (effector/target ratio 1:1), or with a combination of phorbol myristate acetate (PMA) and ionomycin (IONO). Cells were analyzed by ...

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“…Altogether, this orchestra of signaling molecules coordinates the complex process of spiral artery remodeling to maintain a healthy pregnancy. Intriguingly, angiogenic growth factors and cytokines decrease in concentration when uNK cells and trophoblast cells are co-cultured, though the cell type from which these factors are derived in this co-culture is uncertain (Lash et al, 2011). No doubt additional signals will be identified that will further our understanding of uNK cell-trophoblast interactions.…”

Section: Trophoblast-derived Factors Affect Unk Cell Recruitmentmentioning

confidence: 99%

Uterine natural killer cells as modulators of the maternal-fetal vasculature

Matson¹,

Caron²

2014

Int. J. Dev. Biol.

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Precise and local control of the innate immune system within the placenta is an essential component for achieving a normal and healthy pregnancy. One of the most abundant immune cells of the placenta is a subpopulation of natural killer (NK) cells that profusely populates the uterine decidua during early pregnancy. Uterine NK (uNK) cells and trophoblast cells of the placenta communicate both directly and indirectly to contribute to the critical process of spiral artery remodeling. Here, we discuss recent findings that expand our knowledge of uNK cell-trophoblast cell crosstalk and the important role it plays in the maternal vascular adaptation to pregnancy.

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Interaction between uterine natural killer cells and extravillous trophoblast cells: effect on cytokine and angiogenic growth factor production

Cited by 7 publications

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Uterine natural killer cells initiate spiral artery remodeling in human pregnancy

Uterine natural killer cells initiate spiral artery remodeling in human pregnancy

In vivo generation of decidual natural killer cells from resident hematopoietic progenitors

Uterine natural killer cells as modulators of the maternal-fetal vasculature

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