Functions of uterine natural killer cells are mediated by interferon gamma production during murine pregnancy

Ashkar, Ali A.; Croy, B A

doi:10.1006/smim.2000.0319

Cited by 161 publications

(113 citation statements)

References 47 publications

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“…In contrast, 2DL4 was shown to selectively augment IFN-␥ production, but not cytotoxicity, when engaged in resting NK cells (28), suggesting 2DL4 is an activating receptor. The importance of IFN-␥ production by NK cells in decidual development during pregnancy has recently been reported (46). This IFN-␥ stimulatory function was attributed to an unknown interacting protein binding through the transmembrane arginine of 2DL4.…”

Section: Discussionmentioning

confidence: 97%

SHP-1- and Phosphotyrosine-Independent Inhibitory Signaling by a Killer Cell Ig-Like Receptor Cytoplasmic Domain in Human NK Cells

Yusa

Catina

Campbell

2002

The Journal of Immunology

113

146

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Killer cell Ig-like receptors (KIR) are MHC class I-binding immunoreceptors that can suppress activation of human NK cells through recruitment of the Src homology 2-containing protein tyrosine phosphatase-1 (SHP-1) to two immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in their cytoplasmic domains. KIR2DL4 (2DL4; CD158d) is a structurally distinct member of the KIR family, which is expressed on most, if not all, human NK cells. 2DL4 contains only one ITIM in its cytoplasmic domain and an arginine in its transmembrane region, suggesting both inhibitory and activating functions. While 2DL4 can activate IFN-γ production, dependent upon the transmembrane arginine, the function of the single ITIM of 2DL4 remains unknown. In this study, tandem ITIMs of KIR3DL1 (3DL1) and the single ITIM of 2DL4 were directly compared in functional and biochemical assays. Using a retroviral transduction method, we show in human NK cell lines that 1) the single ITIM of 2DL4 efficiently inhibits natural cytotoxicity responses; 2) the phosphorylated single ITIM recruits SHP-2 protein tyrosine phosphatase, but not SHP-1 in NK cells; 3) expression of dominant-negative SHP-1 does not block the ability of 2DL4 to inhibit natural cytotoxicity; 4) surprisingly, mutation of the tyrosine within the single ITIM does not completely abolish inhibitory function; and 5) this correlates with weak SHP-2 binding to the mutant ITIM of 2DL4 in NK cells and a corresponding nonphosphorylated ITIM peptide in vitro. These results reveal new aspects of the KIR-inhibitory pathway in human NK cells, which are SHP-1 and phosphotyrosine independent.

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Section: Discussionmentioning

confidence: 97%

SHP-1- and Phosphotyrosine-Independent Inhibitory Signaling by a Killer Cell Ig-Like Receptor Cytoplasmic Domain in Human NK Cells

Yusa

Catina

Campbell

2002

The Journal of Immunology

113

146

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“…[2][3][4][5] Animal models are of limited use in the analysis of this phenomenon; in particular, trophoblast invasion is much more limited in the mouse uterus, and pre-eclampsia does not occur. The Fas knockout mouse appears to be normally fertile, perhaps because it is mostly uterine natural killer (NK) cells 34 and not trophoblasts 35 that mediate spiral artery transformation in this species.…”

Section: Discussionmentioning

confidence: 99%

Invasive Trophoblasts Stimulate Vascular Smooth Muscle Cell Apoptosis by a Fas Ligand-Dependent Mechanism

Harris

Keogh

Wareing

et al. 2006

The American Journal of Pathology

138

109

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During pregnancy, trophoblasts migrate from the placenta into uterine spiral arteries, transforming them into wide channels that lack vasoconstrictive properties. In pathological pregnancies, this process is incomplete. To define the fundamental events involved in spiral artery remodeling, we have studied the effect of trophoblasts on vascular smooth muscle cells (SMCs). Here we demonstrate for the first time that apoptosis of SMCs can be initiated by invading trophoblasts. When trophoblasts isolated from normal placenta (primary trophoblasts) or conditioned medium was perfused into spiral or umbilical artery segments, apoptosis of SMCs resulted. Culture of human aortic SMCs (HASMCs) with primary trophoblasts, primary trophoblast-conditioned medium, or a trophoblast-derived cell line (SGHPL-4) also significantly increased SMC apoptosis. Fas is expressed by spiral artery SMCs, and a Fas-activating antibody triggered HASMC apoptosis. Furthermore, a Fas ligand (FasL)-blocking antibody significantly inhibited HASMC apoptosis induced by primary trophoblasts, SGHPL-4, or trophoblast-conditioned medium. Depleting primary trophoblast-conditioned medium of FasL also abrogated SMC apoptosis in vessels in situ. These results suggest that apoptosis triggered by the release of soluble FasL from invading trophoblasts contributes to the loss of smooth muscle from the walls of spiral arteries during pregnancy.

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“…Although many factors secreted by uNK cells around the time of remodeling have been implicated as possible triggers of these changes in vascular structure, we focused on the role of uNK cell-produced IFNG (Ashkar et al 2000). Results from alymphoid mice treated with mrIFNG and confirmed in mice with uNK cells lacking the genetic ability to produce IFNG indicated that IFNG alone, independent of the presence of uNK cells, is sufficient to induce SA remodeling (Ashkar et al 2000, Ashkar & Croy 2001. IFNG synthesis by uNK cells is induced in vivo by interleukin 12 (IL12) and enhanced by IL18 , Murphy et al 2009).…”

Section: Roles Of Nk Cells In Physiological Changes To Maternal Samentioning

confidence: 99%

Uterine natural killer cells: supervisors of vasculature construction in early decidua basalis

et al. 2015

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Mammalian pregnancy involves tremendous de novo maternal vascular construction to adequately support conceptus development. In early mouse decidua basalis (DB), maternal uterine natural killer (uNK) cells oversee this process directing various aspects during the formation of supportive vascular networks. The uNK cells recruited to early implantation site DB secrete numerous factors that act in the construction of early decidual vessels (neoangiogenesis) as well as in the alteration of the structural components of newly developing and existing vessels (pruning and remodeling). Although decidual and placental development sufficient to support live births occur in the absence of normally functioning uNK cells, development and structure of implantation site are optimized through the presence of normally activated uNK cells. Human NK cells are also recruited to early decidua. Gestational complications including recurrent spontaneous abortion, fetal growth restriction, preeclampsia, and preterm labor are linked with the absence of human NK cell activation via paternally inherited conceptus transplantation antigens. This review summarizes the roles that mouse uNK cells normally play in decidual neoangiogenesis and spiral artery remodeling in mouse pregnancy and briefly discusses changes in early developmental angiogenesis due to placental growth factor deficiency.Reproduction (2015) 149 R91-R102

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Functions of uterine natural killer cells are mediated by interferon gamma production during murine pregnancy

Cited by 161 publications

References 47 publications

SHP-1- and Phosphotyrosine-Independent Inhibitory Signaling by a Killer Cell Ig-Like Receptor Cytoplasmic Domain in Human NK Cells

SHP-1- and Phosphotyrosine-Independent Inhibitory Signaling by a Killer Cell Ig-Like Receptor Cytoplasmic Domain in Human NK Cells

Invasive Trophoblasts Stimulate Vascular Smooth Muscle Cell Apoptosis by a Fas Ligand-Dependent Mechanism

Uterine natural killer cells: supervisors of vasculature construction in early decidua basalis

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