First Trimester Pregnancy Decidual Natural Killer Cells Contain and Spontaneously Release High Quantities of Granulysin

Vujaklija, Danijela Veljković; Gulić, Tamara; Sučić, Sonja; Nagata, Kazuhiro; Ogawa, Kazuyuki; Laškarin, Gordana; Saito, Shigeru; Haller, Herman; Rukavina, Daniel

doi:10.1111/j.1600-0897.2011.01015.x

Cited by 32 publications

(43 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, dNK express increased levels of the cytolytic molecule granulysin compared to pNK (Koopman et al, 2003). In contrast to pNK, in freshly isolated dNK, granulysin and perforin rarely co-localized (Vujaklija et al, 2013) and dNK but not pNK constitutively secrete granulysin in high levels without prior stimulation (Vujaklija et al, 2011). Granulysin is produced as an inactive 15 kDa pro-peptide that is processed in cytotoxic granules to a 9 kDa membranolytic peptide.…”

Section: A Dnk Paradox – High Levels Of Cytotoxic Granules But Low Cymentioning

confidence: 99%

“…This suggests post-translational modifications that block translation of perforin and granzyme B mRNA into functional proteins that may be mediated by miRNAs (Tilburgs et al, 2010; Trifari et al, 2013). Interestingly, similar to dNK, CD8+ dT express increased levels of granulysin suggesting they are locally activated and may play a protective role against different extracellular or intracellular pathogens (Tilburgs et al, 2010; Vujaklija et al, AJRI 2011; Nakashima et al, 2008). Despite the low levels of cytolytic granules, upon stimulation with PMA, first trimester CD8+ dT were shown to be cytolytic and produce cytokines that affect invasion of trophoblasts (Scaife et al, 2006).…”

Section: Regulation Of Cytolytic Activity Of Cd8+ Dtmentioning

confidence: 99%

See 1 more Smart Citation

Cytotoxic potential of decidual NK cells and CD8+ T cells awakened by infections

Crespo

Zwan

Ramalho‐Santos

et al. 2017

Journal of Reproductive Immunology

View full text Add to dashboard Cite

To establish a healthy pregnancy the maternal immune system must tolerate fetal allo-antigens, yet remain competent to respond to infections. The ability of decidual NK cells (dNK) to promote migration of fetal extravillous trophoblasts (EVT) and placental growth as well as the capacity of EVT to promote immune tolerance are topics of high interest and extensive research. However, the problem of how dNK and decidual CD8+ T cells (CD8+ dT) provide immunity to infections of the placenta and the mechanisms that regulate their cytolytic function has thus far largely been ignored. Fetal EVT are the most invasive cells of the placenta and directly interact with maternal decidual immune cells at this maternal-fetal interface. Besides the expression of non-polymorphic HLA-E and HLA-G molecules that are associated with immune tolerance, EVT also express highly polymorphic HLA-C molecules that can serve as targets for maternal dNK and CD8+ dT responses. HLA-C expression by EVT has a dual role as the main molecule to which immune tolerance needs to be established and as the only molecule that can present pathogen-derived peptides and provide protective immunity when EVT are infected. The focus of this review is to address the regulation of cytotoxicity of dNK and CD8+ dT, which is essential for maternal-fetal immune tolerance as well as recent evidence that both cell types can provide immunity to infections at the maternal-fetal interface. A particular emphasis is given to the role of HLA-C expressed by EVT and its capacity to elicit dNK and CD8+ dT responses.

show abstract

Section: A Dnk Paradox – High Levels Of Cytotoxic Granules But Low Cymentioning

confidence: 99%

Section: Regulation Of Cytolytic Activity Of Cd8+ Dtmentioning

confidence: 99%

Cytotoxic potential of decidual NK cells and CD8+ T cells awakened by infections

Crespo

Zwan

Ramalho‐Santos

et al. 2017

Journal of Reproductive Immunology

View full text Add to dashboard Cite

show abstract

“…Unlike pbNK cells, uNK cells are only weakly cytotoxic against standard cancer cell lines (e.g., K562) and do not normally kill trophoblast cells (46)(47)(48). This is somewhat of a puzzle, as uNK cells are large lymphocytes with prominent cytoplasmic granules containing perforin, granzymes, and granulysin, which suggests that other, noncytolytic functions of these proteins are important (49)(50)(51). Although uNK cells do not normally kill, they might become cytolytic in certain situations, such as CMV infection in which cellular stress is detected by the NKG2D receptor (52).…”

Section: Figurementioning

confidence: 99%

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

Moffett¹,

Colucci²

2014

J. Clin. Invest.

337

313

View full text Add to dashboard Cite

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

show abstract

mentioning

confidence: 99%

“…12 Granulysin is expressed in human decidual lymphocytes (DLs) in two forms 13 and is profusely secreted from these cells. 12 The 15-kDa granulysin precursor shows immunomodulatory properties and enhances immune response, whereas the shorter 9-kDa form of granulysin directly participates in the lysis of prokaryotic cells and apoptosis of eukaryotic cells. 14,15 IL-15 increases the intracellular setting of perforin and 15-kDa granulysin proteins along with marker of degranulation, lysosomal-associated membrane protein-1 (LAMP-1) in DLs, indicating the formation of effector granules with secretory and cytolytic potential.…”

mentioning

confidence: 99%

Potential role of heat‐shock protein 70 and interleukin‐15 in the pathogenesis of threatened spontaneous abortions

Gulić

Laškarin

Dominović

et al. 2016

American J Rep Immunol

Self Cite

View full text Add to dashboard Cite

show abstract

First Trimester Pregnancy Decidual Natural Killer Cells Contain and Spontaneously Release High Quantities of Granulysin

Abstract: Abundant expression of GNLY in the decidual immunocompetent cells and the capacity of decidual CD56(+) cells to spontaneously secrete high quantities of GNLY point to important protective and immunomodulatory role that this molecule could play at the maternal-fetal interface.

Cited by 32 publications

References 26 publications

Cytotoxic potential of decidual NK cells and CD8+ T cells awakened by infections

Cytotoxic potential of decidual NK cells and CD8+ T cells awakened by infections

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

Potential role of heat‐shock protein 70 and interleukin‐15 in the pathogenesis of threatened spontaneous abortions

Contact Info

Product

Resources

About