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. 2019 Jul 2;8:F1000 Faculty Rev-999. [Version 1] doi: 10.12688/f1000research.19132.1

Table 1. Cytokines, chemokines, and growth factor production by uterine natural killer cells.

Publication Cytokines, chemokines, and growth factors detected Cell preparation Gestational age Conditions
El Costa et al. 45 IFNγ, TNFα, MIP-1α, MIP-1β, GM-CSF MACS-negative selection, 96% CD3−CD56+ 8–12 weeks Engagement of NKp30 (but not
NKp46)
Higuma-Myojo
et al. 79
TGF, minor populations of CD56+ cells producing other
cytokines
Ficoll, flow cytometry 6–12 weeks Mononuclear cells stimulated with
PMA/ionomycin/brefeldin 4 hours,
flow cytometry
Lash et al. 38 Ang1, Ang2, PDGF-BB (low), KGF (low), ICAM-1 (low),
VEGF-C, PlGF, TGFβ1
MACS-positive selection, >95% CD56+ 8–10 weeks, 12–14
weeks
No stimulation, Fastquant, ELISA
Lash et al. 39 IL-1β, IL-4, IL-6, IL-8, IL-10, IL-13, GM-CSF, IFNγ,
RANTES, TNFα
MACS-positive selection >95% CD56+ 8–10 weeks, 12–14
weeks
No stimulation, Fastquant, ELISA
Hanna et al. 66 CXCL8 (IL-8), CXCL10 (IP-10), CCL5 (RANTES), CCL22,
MIP-1α, MIP-1β, PlGF, VEGF-A, VEGF-B, VEGF-C
Flow cytometry cell sorting, >99% CD56 bright
CD16−CD3−
First trimester IL-15 72 hours
Sotnikova et al. 62 IFNγ Dynabeads-positive selection 7–10 weeks Incubation with autologous
cytotrophoblast
Engert et al. 80 GRO, MCP1, I-309, RANTES, IL-8, IL-1β, EGF, VEGF,
TPO, M-CSF, ENA, oncostatin M, IL-10, GROα,
angiogenin, IL-1α, IL-4, IL-12p40p70, IFNγ, SCF, SDF-1,
MCP-2 (detected in >50% samples)
MACS, >90% pure 7–8 weeks No stimulation, protein array
Saito et al. 81 G-CSF, GM-CSF, M-CSF, TNFα, IFNγ, LIF Flow cytometry sorting 7–9 weeks No stimulation
Fraser et al. 82 CXCL16, HB-EGF, HGF, IL-1β, IL-8, TGFβ1, UPA, TIMP-1 MACS-positive selection, 93.6 ± 1.3% CD56 +,
80 ± 4% viability after 24 hours
9.1–13.7 weeks IL-15, SCF
Wallace et al. 83 IL-6, IL-8, CXCL10 MagCellect-negative selection, CD56+ 95.7 ±
0.92%, viability after 6 hours 84.6 ± 2.8%
8–14 weeks IL-15, SCF
Wallace et al. 84 Angiogenin, sIL2-R, endostatin, PlGF, IL-1RA, MIG, MIP-
1α, MIP-1β, RANTES
MACS-positive selection, 93.6 ± 1.3% CD56+ 9–14 weeks IL-15, SCF
Wallace et al. 85 TNFα, CXCL10, IFNγ, IL-8, PlGF (mRNA) MagCellect-negative selection, CD56+ 95.7 ±
0.92%, viability after 6 hours 84.6 ± 2.8%
9–14 weeks IL-15, SCF
Kennedy et al. 63 GM-CSF, CCL3, CCL1, XCL1 Flow cytometry and intracellular cytokine
detection; or MACS positive selection and
ELISA
First trimester Activation of KIR2DS4
Chen et al. 86 Angiogenin, bFGF, VEGF-A, VEGFR, IL-1α MACS-positive selection, 91.3%
CD16−CD56+
LH+7 non-pregnant
endometrium
Fu et al. 65 Pleiotrophin, osteopontin, osteoglycin Ficoll, MACS-negative selection First trimester Co-culture with EVT

Ang, angiopoetin; bFGF, basic fibroblast growth factor; CCL, C-C motif chemokine; EGF, epidermal growth factor; ELISA, enzyme-

linked immunosorbent assay; ENA, epithelial neutrophil-activating protein; EVT, extravillous trophoblast; G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte-macrophage colony-stimulating factor; GRO, growth-regulated oncogene; HB-EGF, heparin-binding epidermal growth factor; HGF, hepatocyte growth factor; ICAM-1, intercellular adhesion molecule 1; IFN, interferon; IL, interleukin; KGF, keratinocyte growth factor; LIF, leukocyte inhibitory factor; MACS, magnetic-activated cell sorting; MCP, monocyte chemotactic protein; M-CSF, macrophage colony-stimulating factor; MIG, monokine induced by interferon-gamma; MIP, macrophage inflammatory protein; PDGF-BB, platelet-derived growth factor beta; PlGF, placental growth factor; RANTES, regulated upon activation, normal T cell expressed, and secreted; SCF, stem cell factor; SDF-1, stromal cell-derived factor 1; sIL2-R, soluble interleukin-2 receptor; TGF, transforming growth factor; TIMP-1, tissue inhibitor of metalloproteinase 1; TNFα, tumor necrosis factor alpha; TPO, thrombopoietin; UPA, urokinase-type plasminogen activator; VEGF, vascular endothelial growth factor; VEGFR, vascular endothelial growth factor receptor.