Natural killer cell in the developing life

2015 ◽  
Vol 43 (1) ◽  
Author(s):  
Yen-Chang Lee ◽  
Syh-Jae Lin
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Immune Cells ◽  
Killer Cell ◽  
Immune Defense ◽  
Innate Immune ◽  
First Line ◽  
Successful Pregnancy ◽  
Neonatal Stage

AbstractNatural killer (NK) cells that provide first-line innate immune reactions against virus-infected and tumor cells have different roles in different body sites and in different stages. From the beginning of life, NK cells participate in many aspects of development, especially in a successful pregnancy and a healthy neonatal stage. This article reviews recent advances regarding the role of NK cells in implantation, placentation and immune tolerance during pregnancy as well as in the neonatal immune defense. The interactions between NK cells and other immune cells in each developmental stage are discussed.

Natural Killer Cells Induce the Formation of Neutrophil Extracellular Traps (NETs) in Venous Thrombosis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1424-1424
Author(s):  
François-René Bertin ◽  
Sandrine Laurance ◽  
Catherine Lemarie ◽  
Mark Blostein
Keyword(s):  
Venous Thrombosis ◽  
Nk Cells ◽  
Natural Killer ◽  
Immune Cells ◽  
Neutrophil Extracellular Traps ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Flow Restriction ◽  
Extracellular Traps

Abstract Thrombosis is considered to be a pathological deviation of physiologic hemostasis involving similar mechanisms. Interestingly, recent work demonstrates that innate immune cells promote venous thrombosis. Innate immune cells were shown to collaborate to induce the activation of the coagulation cascade and platelets. In particular, neutrophils contribute to venous thrombosis through the release of neutrophil extracellular traps (NETs). However, the mechanism triggering the formation of NETs during venous thrombosis remain unknown. Of interest, a study showed that IFNγ induced the formation of NETs. Thus, we investigated the role of IFNγ-producing cells in the development of thrombosis. We used mice lacking IFNγ, Tbet (the transcription factor regulating the expression of IFNγ) or wild type mice. Venous thrombosis was induced using the flow restriction model in the inferior vena cava , as has been previously published. In Tbet-/-, IFNγ-/- and WT mice, we show that the absence of Tbet or IFNγ decreases the formation of thrombi after venous thrombosis induction, suggesting that the Tbet+/IFNγ producing cells are required for the early development of venous thrombosis. Comparing the composition of the thrombi from Tbet-/-, IFNγ-/- and WT mice, we show that, in all mice, neutrophils are the main cellular component of thrombi followed by monocytes; however, the number of neutrophil extracellular traps (NETs) formed during thrombosis is significantly lower in Tbet-/- and IFNγ-/- mice. Furthermore, NET formation is also decreased in WT mice specifically depleted of IFNγ and increases in Tbet-/- and IFNγ-/- mice injected with recombinant IFNγ. In vitro, we show that stimulation of WT murine neutrophils with recombinant IFNγ triggers the formation of NETs demonstrating that Tbet and IFNγ are crucial for NET formation by neutrophils. Natural killer (NK) cells are the main producers of IFNγ . Thus, we investigated the role of NK cells in venous thrombosis induced by flow restriction. NK cells were specifically depleted with an antibody during the development of venous thrombosis. The absence of NK cells results in smaller thrombi suggesting that NK cells are required for early thrombus development. Additionally, depletion in NK cells results in decreased in-situ IFNγ production and decreased NET formation. To directly link NK cells to the formation of NETs, WT neutrophils were co-cultured with Tbet-/- and IFNγ-/- NK cells. We show that WT neutrophils release less NETs when cultured with Tbet-/- and IFNγ-/- NK cells as compared to WT NK cells. These data suggest that NK cells trigger the formation of NETs by neutrophils through the production of IFNγ. Hence, we demonstrate that, in a partial flow restriction model of venous thrombosis, Tbet and IFNγ are crucial for thrombus development by promoting the formation of NETs by neutrophils and that NK cells are key effector cells in this process. Disclosures Blostein: boehringer-ingelheim: Research Funding.

scholarly journals Neonatal Natural Killer Cell Function: Relevance to Antiviral Immune Defense

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Yen-Chang Lee ◽  
Syh-Jae Lin
Keyword(s):  
Natural Killer ◽  
Cell Function ◽  
Killer Cell ◽  
Immune Defense ◽  
Innate Immune ◽  
Clinical Implications ◽  
Natural Killer Cell Function ◽  
First Line ◽  
Innate And Adaptive Immunity ◽  
Infected Cells

Neonates are particularly susceptible to various pathogens compared to adults, which is attributed in part to their immature innate and adaptive immunity. Natural killer cells provide first-line innate immune reactions against virus-infected cells without prior sensitization. This review updates phenotypic and functional deficiencies of neonatal cells compared to their adult counterparts and their clinical implications.

scholarly journals Prognostic significance of natural killer cell-associated markers in gastric cancer: quantitative analysis using multiplex immunohistochemistry

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Hee Young Na ◽  
Yujun Park ◽  
Soo Kyung Nam ◽  
Jiwon Koh ◽  
Yoonjin Kwak ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
B Cells ◽  
Nk Cells ◽  
Natural Killer ◽  
Immune Cells ◽  
Nk Cell ◽  
Critical Role ◽  
Killer Cell ◽  
Prognostic Significance

Abstract Background Natural killer (NK) cells mediate the anti-tumoral immune response as an important component of innate immunity. The aim of this study was to investigate the prognostic significance and functional implication of NK cell-associated surface receptors in gastric cancer (GC) by using multiplex immunohistochemistry (mIHC). Methods We performed an mIHC on tissue microarray slides, including 55 GC tissue samples. A total of 11 antibodies including CD57, NKG2A, CD16, HLA-E, CD3, CD20, CD45, CD68, CK, SMA, and ki-67 were used. CD45 + CD3-CD57 + cells were considered as CD57 + NK cells. Results Among CD45 + immune cells, the proportion of CD57 + NK cell was the lowest (3.8%), whereas that of CD57 + and CD57- T cells (65.5%) was the highest, followed by macrophages (25.4%), and B cells (5.3%). CD57 + NK cells constituted 20% of CD45 + CD57 + immune cells while the remaining 80% were CD57 + T cells. The expression of HLA-E in tumor cells correlated with that in tumoral T cells, B cells, and macrophages, but not CD57 + NK cells. The higher density of tumoral CD57 + NK cells and tumoral CD57 + NKG2A + NK cells was associated with inferior survival. Conclusions Although the number of CD57 + NK cells was lower than that of other immune cells, CD57 + NK cells and CD57 + NKG2A + NK cells were significantly associated with poor outcomes, suggesting that NK cell subsets play a critical role in GC progression. NK cells and their inhibitory receptor, NKG2A, may be potential targets in GC.

scholarly journals Natural Killer Cells: Potential Biomarkers and Therapeutic Target in Autoimmune Diseases?

2021 ◽  
Vol 12 ◽  
Author(s):  
Elena Gianchecchi ◽  
Domenico V. Delfino ◽  
Alessandra Fierabracci
Keyword(s):  
Systemic Sclerosis ◽  
Autoimmune Diseases ◽  
Cytotoxic Activity ◽  
Nk Cells ◽  
Natural Killer ◽  
T Cell Activation ◽  
Cell Activation ◽  
Nk Cell ◽  
Killer Cell

Autoimmune diseases recognize a multifactorial pathogenesis, although the exact mechanism responsible for their onset remains to be fully elucidated. Over the past few years, the role of natural killer (NK) cells in shaping immune responses has been highlighted even though their involvement is profoundly linked to the subpopulation involved and to the site where such interaction takes place. The aberrant number and functionality of NK cells have been reported in several different autoimmune disorders. In the present review, we report the most recent findings regarding the involvement of NK cells in both systemic and organ-specific autoimmune diseases, including type 1 diabetes (T1D), primary biliary cholangitis (PBC), systemic sclerosis, systemic lupus erythematosus (SLE), primary Sjögren syndrome, rheumatoid arthritis, and multiple sclerosis. In T1D, innate inflammation induces NK cell activation, disrupting the Treg function. In addition, certain genetic variants identified as risk factors for T1D influenced the activation of NK cells promoting their cytotoxic activity. The role of NK cells has also been demonstrated in the pathogenesis of PBC mediating direct or indirect biliary epithelial cell destruction. NK cell frequency and number were enhanced in both the peripheral blood and the liver of patients and associated with increased NK cell cytotoxic activity and perforin expression levels. NK cells were also involved in the perpetuation of disease through autoreactive CD4 T cell activation in the presence of antigen-presenting cells. In systemic sclerosis (SSc), in addition to phenotypic abnormalities, patients presented a reduction in CD56hi NK-cells. Moreover, NK cells presented a deficient killing activity. The influence of the activating and inhibitory killer cell immunoglobulin-like receptors (KIRs) has been investigated in SSc and SLE susceptibility. Furthermore, autoantibodies to KIRs have been identified in different systemic autoimmune conditions. Because of its role in modulating the immune-mediated pathology, NK subpopulation could represent a potential marker for disease activity and target for therapeutic intervention.

scholarly journals CD69 Deficiency Enhances the Host Response to Vaccinia Virus Infection through Altered NK Cell Homeostasis

2016 ◽  
Vol 90 (14) ◽  
pp. 6464-6474 ◽  
Author(s):  
Laura Notario ◽  
Elisenda Alari-Pahissa ◽  
Antonio de Molina ◽  
Pilar Lauzurica
Keyword(s):  
Immune Response ◽  
Infection Control ◽  
Vaccinia Virus ◽  
Nk Cells ◽  
Natural Killer ◽  
Host Response ◽  
Nk Cell ◽  
Innate Immune ◽  
Cell Numbers

ABSTRACTDuring the host response to viral infection, the transmembrane CD69 protein is highly upregulated in all immune cells. We have studied the role of CD69 in the murine immune response to vaccinia virus (VACV) infection, and we report that the absence of CD69 enhances protection against VACV at both short and long times postinfection in immunocompetent and immunodeficient mice. Natural killer (NK) cells were implicated in the increased infection control, since the differences were greatly diminished when NK cells were depleted. This role of NK cells was not based on an altered NK cell reactivity, since CD69 did not affect the NK cell activation threshold in response to major histocompatibility complex class I NK cell targets or protein kinase C activation. Instead, NK cell numbers were increased in the spleen and peritoneum of CD69-deficient infected mice. That was not just secondary to better infection control in CD69-deficient mice, since NK cell numbers in the spleens and the blood of uninfected CD69−/−mice were already augmented. CD69-deficient NK cells from infected mice did not have an altered proliferation capacity. However, a lower spontaneous cell death rate was observed for CD69−/−lymphocytes. Thus, our results suggest that CD69 limits the innate immune response to VACV infection at least in part through cell homeostatic survival.IMPORTANCEWe show that increased natural killer (NK) cell numbers augment the host response and survival after infection with vaccinia virus. This phenotype is found in the absence of CD69 in immunocompetent and immunodeficient hosts. As part of the innate immune system, NK lymphocytes are activated and participate in the defense against infection. Several studies have focused on the contribution of NK cells to protection against infection with vaccinia virus. In this study, it was demonstrated that the augmented early NK cell response in the absence of CD69 is responsible for the increased protection seen during infection with vaccinia virus even at late times of infection. This work indicates that the CD69 molecule may be a target of therapy to augment the response to poxvirus infection.

scholarly journals Natural killer cells suppress human erythroid stem cell proliferation in vitro

Blood ◽  
1984 ◽  
Vol 63 (2) ◽  
pp. 260-269 ◽  
Author(s):  
KF Mangan ◽  
ME Hartnett ◽  
SA Matis ◽  
A Winkelstein ◽  
T Abo
Keyword(s):  
Stem Cell ◽  
Natural Killer Cell ◽  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Killer Cell ◽  
Human Natural Killer Cell ◽  
Percoll Density Gradient Centrifugation

Abstract To determine the role of natural killer (NK) cells in the regulation of human erythropoiesis, we studied the effects of NK-enriched cell populations on the in vitro proliferation of erythroid stem cells at three different levels of maturation (day 14 blood BFU-E, day 5–6 marrow CFU-E, and day 10–12 marrow BFU-E). NK cells were enriched from blood by Percoll density gradient centrifugation and by fluorescence- activated cell sorting (FACS), using the human natural killer cell monoclonal antibody, HNK-1. The isolated enriched fractions were cocultured with autologous nonadherent marrow cells or blood null cells and erythropoietin in a methylcellulose erythroid culture system. Cells from low-density Percoll fractions (NK-enriched cells) were predominantly large granular lymphocytes with cytotoxic activity against K562 targets 6–10-fold greater than cells obtained from high- density Percoll fractions (NK-depleted cells). In coculture with marrow nonadherent cells (NA) at NK:NA ratios of 2:1, NK-enriched cells suppressed day 5–6 CFU-E to 62% (p less than 0.025) of controls, whereas NK-depleted cells slightly augmented CFU-E to 130% of controls (p greater than 0.05). In contrast, no suppression of day 10–12 marrow BFU-E was observed employing NK-enriched cells. The NK CFU-E suppressor effects were abolished by complement-mediated lysis of NK-enriched cells with the natural killer cell antibody, HNK-1. Highly purified HNK- 1+ cells separated by FACS suppressed marrow CFU-E to 34% (p less than 0.025) and marrow BFU-E to 41% (p less than 0.025) of controls. HNK- cells had no significant effect on either BFU-E or CFU-E growth. NK- enriched cells were poor stimulators of day 14 blood BFU-E in comparison to equal numbers of NK-depleted cells or T cells isolated by E-rosetting (p less than 0.01). Interferon boosting of NK-enriched cells abolished their suboptimal burst-promoting effects and augmented their CFU-E suppressor effects. These studies provide evidence for a potential regulatory role of NK cells in erythropoiesis. The NK suppressor effect is maximal at the level of the mature erythroid stem cell CFU-E. These findings may explain some hypoproliferative anemias that develop in certain NK cell-activated states.

Natural killer cells and T lymphocytes in pregnancy and pre-eclampsia

2017 ◽  
Vol 131 (24) ◽  
pp. 2911-2917 ◽  
Author(s):  
Erin B. Taylor ◽  
Jennifer M. Sasser
Keyword(s):  
Natural Killer ◽  
T Lymphocyte ◽  
Immune Cells ◽  
Experimental Models ◽  
Innate Immune ◽  
Hypertensive Disorder ◽  
Hypertensive Disorder Of Pregnancy ◽  
Lymphocyte Populations ◽  
In Pregnancy

Although pre-eclampsia (PE), a hypertensive disorder of pregnancy, has significant maternal and fetal morbidity and mortality worldwide, the mechanisms contributing to this disease have not been fully elucidated. Studies in patients and experimental models have shown that changes in the number or function of immune cells of both the adaptive and innate immune systems contribute to the development and pathogenesis of PE. This commentary summarizes our current understanding of the role of the immune system in the pathogenesis of PE, specifically focussing on dysfunction of natural killer (NK) cells and T lymphocyte populations.

Enhancement of Natural Killer Cell Interferon-Gamma Production By the Derivatives of the Natural Product Phyllanthusmins Via TLR-Mediated NF-Kb and STAT3 Signaling Pathways

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1031-1031
Author(s):  
Luxi Chen ◽  
Long Yi ◽  
Yuning Ren ◽  
Jianying Zhang ◽  
A. Douglas Kinghorn ◽  
...  
Keyword(s):  
Nk Cells ◽  
Signaling Pathways ◽  
Natural Product ◽  
Natural Killer ◽  
Nk Cell ◽  
Conflicts Of Interest ◽  
Killer Cell ◽  
Immune Defense ◽  
Ifn Gamma ◽  
Stat3 Signaling

Abstract Natural killer (NK) cells are known to play a pivotal role in regulating immune defense against tumors and viruses. However, very few studies describe the effects of natural products or their derivatives on NK cell function. We previously showed that the natural product lignan phyllanthusmin C enhances human NK cell IFN-gamma production. In this study, we successfully synthesized dozens of phyllanthusmin derivatives and screened their activities to enhance IFN-gamma production by NK cells. We found that three of these derivatives possessed capacities to induce IFN-gamma production by NK cells. Among them, derivative No. 17 had the highest efficacy and was significantly superior (P < 0.05) to that of the original phyllanthusmin C. These three phyllanthusmin derivatives had no adverse effect on human NK cell survival or proliferation. All derivatives alone or in combination with IL-12 or IL-15 induced human NK cell interferon (IFN)-gamma in comparison with the corresponding vehicle control or cytokine alone (P < 0.05). These derivatives stimulated IFN-gamma production in both CD56bright and CD56dim human NK cell subsets (P < 0.01). Mechanistically, immunoblotting assays and chromatin immunoprecipitation (ChIP) analyses combined with promoter-reporter luciferase assays revealed that these phyllanthusmin derivatives induced the phosphorylation of NF-κB and STAT3, resulting in their increased binding on theIFN G promoter, which was dependent on the Toll-like receptor (TLR) 1 and the TLR3 signaling pathways, respectively. STAT3 knockdown with lentivirus shRNA and inhibition of NF-kB signaling with a specific inhibitor (TPCK) significantly attenuated IFN-gamma production induced by these phyllanthusmin derivatives in human NK cells (P < 0.05). Blockade of TLR1 or TLR3 with their corresponding neutralizing antibodies nearly abolished activation of NF-κB or STAT3 as well as IFN-γ induction by the phyllanthusmin derivatives (P < 0.05). In conclusion, we have successfully synthesized and screened phyllanthusmin derivatives and identified three compounds that induce IFN-gamma production in human NK cells, one of which had optimal potential. The induction of human NK cell IFN-gamma production by phyllanthusmin derivatives is mediated by TLR1-NF-κB and TLR3-STAT3 signaling pathways, rendering their potential for use as agents for cancer prevention or treatment. Disclosures No relevant conflicts of interest to declare.

The role of IL-17 producing NK cells and other innate immune cells in poly(I:C) triggered exacerbation of experimental asthma

2016 ◽  
Author(s):  
Lars Lunding ◽  
Christina Vock ◽  
Sina Webering ◽  
Jochen Behrends ◽  
Christoph Hölscher ◽  
...  
Keyword(s):  
Nk Cells ◽  
Immune Cells ◽  
Innate Immune ◽  
Poly I:C ◽  
Innate Immune Cells

scholarly journals Human Herpesvirus 6B Downregulates Expression of Activating Ligands during Lytic Infection To Escape Elimination by Natural Killer Cells

2016 ◽  
Vol 90 (21) ◽  
pp. 9608-9617 ◽  
Author(s):  
Dominik Schmiedel ◽  
Julie Tai ◽  
Francesca Levi-Schaffer ◽  
Sarah Dovrat ◽  
Ofer Mandelboim
Keyword(s):  
Immune System ◽  
Nk Cells ◽  
Natural Killer ◽  
Immune Cells ◽  
Human Herpesvirus ◽  
Innate Immune ◽  
Human Herpesvirus 6 ◽  
Content Type ◽  
Life Threatening ◽  
Infected Cells

ABSTRACT The Herpesviridae family consists of eight viruses, most of which infect a majority of the human population. One of the less-studied members is human herpesvirus 6 (HHV-6) ( Roseolovirus ), which causes a mild, well-characterized childhood disease. Primary HHV-6 infection is followed by lifelong latency. Reactivation frequently occurs in immunocompromised patients, such as those suffering from HIV infection or cancer or following transplantation, and causes potentially life-threatening complications. In this study, we investigated the mechanisms that HHV-6 utilizes to remain undetected by natural killer (NK) cells, which are key participants in the innate immune response to infections. We revealed viral mechanisms which downregulate ligands for two powerful activating NK cell receptors: ULBP1, ULBP3, and MICB, which trigger NKG2D, and B7-H6, which activates NKp30. Accordingly, this downregulation impaired the ability of NK cells to recognize HHV-6-infected cells. Thus, we describe for the first time immune evasion mechanisms of HHV-6 that protect lytically infected cells from NK elimination. IMPORTANCE Human herpesvirus 6 (HHV-6) latently infects a large portion of the human population and can reactivate in humans lacking a functional immune system, such as cancer or AIDS patients. Under these conditions, it can cause life-threatening diseases. To date, the actions and interplay of immune cells, and particularly cells of the innate immune system, during HHV-6 infection are poorly defined. In this study, we aimed to understand how cells undergoing lytic HHV-6 infection interact with natural killer (NK) cells, innate lymphocytes constituting the first line of defense against viral intruders. We show that HHV-6 suppresses the expression of surface proteins that alert the immune cells by triggering two major receptors on NK cells, NKG2D and NKp30. As a consequence, HHV-6 can replicate undetected by the innate immune system and potentially spread infection throughout the body. This study advances the understanding of HHV-6 biology and the measures it uses to successfully escape immune elimination.

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