The Fetal Allograft Revisited: Does the Study of an Ancient Invertebrate Species Shed Light on the Role of Natural Killer Cells at the Maternal-Fetal Interface?

Lightner, Amy L.; Schust, Danny J.; Chen, Yi Bin A.; Barrier, Breton F.

doi:10.1155/2008/631920

Cited by 11 publications

(7 citation statements)

References 75 publications

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“…Indeed, the intimate contact between maternal immune and trophoblast cells in pregnancy is the only natural situation in mammals in which allogeneic cells breach epithelial boundaries and come into direct contact (Figure 1). In invertebrates, NK-like allorecognition operates to determine whether fusion of individual colonial forms occur, a situation that has resonance with the demarcation of the maternal-fetal interface (76).…”

Section: Nk Cell Allorecognition In Transplantation and Pregnancymentioning

confidence: 99%

Uterine NK cells: active regulators at the maternal-fetal interface

Moffett¹,

Colucci²

2014

J. Clin. Invest.

341

301

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Pregnancy presents an immunological conundrum because two genetically different individuals coexist. The maternal lymphocytes at the uterine maternal-fetal interface that can recognize mismatched placental cells are T cells and abundant distinctive uterine NK (uNK) cells. Multiple mechanisms exist that avoid damaging T cell responses to the fetus, whereas activation of uNK cells is probably physiological. Indeed, genetic epidemiological data suggest that the variability of NK cell receptors and their MHC ligands define pregnancy success; however, exactly how uNK cells function in normal and pathological pregnancy is still unclear, and any therapies aimed at suppressing NK cells must be viewed with caution. Allorecognition of fetal placental cells by uNK cells is emerging as the key maternalfetal immune mechanism that regulates placentation. The maternal-fetal interface in the uterusThe immunological paradox of pregnancy became a central preoccupation of immunologists after the discovery of acquired immunological tolerance (1). Pregnancy and transplantation were instrumental in the discovery of MHC polymorphisms, since the best natural producers of alloantibodies against HLA molecules are multiparous women (2) and polytransfused individuals (3). Since Medawar's influential essay (4), the focus for immunologists has been how maternal T cells become tolerant of the fetal allograft. The current state of this field has been summarized in recent scholarly reviews (5, 6). We have taken a different approach that arose from studying pregnancy disorders, which affect millions of women and are a persistent global health problem. This view of the maternal immune system arose from considering how placentation evolved in mammals and is centered on the anatomy, physiology, and pathology of the pregnant uterus. We focus on the immune cells present in the pregnant uterine lining, the decidua, dominated by NK cells (known as decidual NK cells or uterine NK

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Section: Nk Cell Allorecognition In Transplantation and Pregnancymentioning

confidence: 99%

Uterine NK cells: active regulators at the maternal-fetal interface

Moffett¹,

Colucci²

2014

J. Clin. Invest.

341

301

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“…Thus, distinct functional counterparts arising from a common origin, serve distinct immunologic functions, one based upon recognition of self and a second on phylogenetically distinct, non‐self, forms. The evolution of MHC molecules with an expanded capacity to present non‐self antigen coevolved with the development of adaptive immunity . We now include a wide array of MHC‐unrelated non‐self (pathogen) recognizing molecules within the innate immune system because they do not undergo genetic rearrangement.…”

Section: Innate Versus Adaptive Immunity: Self Versus Non‐selfmentioning

confidence: 99%

The Multiple Faces of the Decidual Natural Killer Cell

Winger¹,

Reed²

2013

American J Rep Immunol

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The decidual NK (dNK) cell is called on to support placental growth by providing an array of growth factors that directly transform the spiral artery and direct trophoblast invasion. Successful transformation is dependent upon adequate stimulation paradoxically stimulating the cell for placental support rather than cytotoxicity. With the identification of its supportive role, the presence of an intact cytotoxic mechanism has been confusing. Investigators have found that the cell remains fully capable of cytotoxic responses particularly in response to pathogen-specific signals. We postulate a dual threshold model where moderate stimulation results in release of stimulatory factors supporting placentation while intense stimulation, particularly triggered through pathogen-specific receptors, restores the cell to its protective, cytotoxic, role. Individual dNK cells mature attaining the capacity to respond to the delivery of cognate signals. The process, known as 'licensing' tunes responsiveness to the degree to which stochastically selected inhibitory receptors block cytotoxic response to self. A changing licensing milieu within the decidua may result in altered and unsuitable receptor expression. We postulate that a heterogeneous population of dNK cells where cells inappropriately licensed for the milieu contributes to pathology.

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“…These animals, along with B. schlosseri, can be used to study the evolution of the immune system and could serve as models for screening new therapeutics targeting cellular immunity and transplant rejection. The star ascidian has also been suggested to serve as a model for maternal-fetus allorecognition issues, as the organism has a natural killer (NK) cell similar to human uterine NK cells (Lightner et al 2008). …”

Section: Allorecognition and Adaptive Immune Systemmentioning

confidence: 99%

Invertebrate Models for Biomedical Research, Testing, and Education

Wilson-Sanders

2011

ILAR Journal

101

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Invertebrate animals have been used as medicinals for 4,000 years and have served as models for research and teaching since the late 1800s. Interest in invertebrate models has increased over the past several decades as the research community has responded to public concerns about the use of vertebrate animals in research. As a result, invertebrates are being evaluated and recognized as models for many diseases and conditions. Their use has led to discoveries in almost every area of biology and medicine--from embryonic development to aging processes. Species range from terrestrial invertebrates such as nematodes and insects to freshwater and marine life including planarians, crustaceans, molluscs, and many others. The most often used models are the fruit fly Drosophila melanogaster and the minuscule nematode Caenorhabditis elegans. Topics in this article are categorized by biologic system, process, or disease with discussion of associated invertebrate models. Sections on bioactive products discovered from invertebrates follow the models section, and the article concludes with uses of invertebrates in teaching. The models reviewed can serve as references for scientists, researchers, veterinarians, institutional animal care and use committees (IACUCs), and others interested in alternatives to vertebrate animals.

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The Fetal Allograft Revisited: Does the Study of an Ancient Invertebrate Species Shed Light on the Role of Natural Killer Cells at the Maternal-Fetal Interface?

Cited by 11 publications

References 75 publications

Uterine NK cells: active regulators at the maternal-fetal interface

Uterine NK cells: active regulators at the maternal-fetal interface

The Multiple Faces of the Decidual Natural Killer Cell

Invertebrate Models for Biomedical Research, Testing, and Education

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