Role Of Natural Killer Cells Research Articles

The Role of Natural Killer Cells and Their Metabolism in HIV-1 Infection.

Natural killer (NK) cells are multifaceted innate effector cells that critically influence antiviral immunity, and several protective NK cell features that modulate HIV-1 acquisition and viral control have been described. Chronic HIV-1 infection leads to NK cell impairment that has been associated with metabolic dysregulations. Therapeutic approaches targeting cellular immune metabolism represent potential novel interventions to reverse defective NK cell function in people living with HIV.

The Role of Natural Killer Cells in Oncolytic Virotherapy: Friends or Foes?

Oncolytic virotherapy (OVT) has emerged as a promising cancer immunotherapy, and is capable of potentiating other immunotherapies due to its capacity to increase tumor immunogenicity and to boost host antitumor immunity. Natural killer (NK) cells are a critical cellular component for mediating the antitumor response, but hold a mixed reputation for their role in mediating the therapeutic efficacy of OVT. This review will discuss the pros and cons of how NK cells impact OVT, and how to harness this knowledge for the development of effective strategies that could modulate NK cells to improve OVT-based therapeutic outcomes.

SAT-544 Study on the role of natural killer cells in chronic hepatitis B patients treated with intermittent interferon therapy

SAT-544 Study on the role of natural killer cells in chronic hepatitis B patients treated with intermittent interferon therapy

Investigating the role of Natural Killer cells in the control of latent Epstein-Barr virus infection

Abstract Epstein–Barr virus (EBV) is a ubiquitous gamma-herpesvirus that persists as a chronic, asymptomatic infection in over 90% of the adult population with the virus transitioning to latency in a subset of memory B cells. Failure to control latent EBV can result in a variety of malignancies, including lymphoproliferative diseases. Studies in experimental models and humans suggest that NK cells are critical in the host defense against EBV. Previously, we demonstrated NK cells expressing the inhibitory receptor NKG2A were specifically able to recognize and kill autologous EBV-lymphoblastoid cell lines (EBV-LCL). We also showed that HLA-E-presented peptides derived from latent EBV proteins can impair NKG2A recognition and signaling, potentially leading to NK cell activation. To better understand the phenotype of NK cells that respond to latent EBV, we generated a panel of EBV-LCL and performed co-culture experiments with primary NK cells and autologous EBV-LCL. We developed a novel mass cytometry panel and found that in addition to NKG2A, EBV-LCL-responsive NK cells express increased NKp30 and CD32 and decreased CD16 which may contribute to NK cell activation and killing of EBV-LCL. Further, we generated HLA-E knockout EBV-LCL using CRISPR and determined that autologous NK cell cytotoxicity increased, suggesting that disrupting the NKG2A:HLA-E immune checkpoint axis enhances killing of EBV-infected B cells and would be an attractive therapeutic option for EBV-associated malignancies.

The Role of Natural Killer Cells in the Tumor Immune Microenvironment of EBV-Associated Nasopharyngeal Carcinoma.

Endemic nasopharyngeal carcinoma (NPC) is closely associated with the Epstein-Barr virus (EBV), which contributes to tumor development and influences the tumor immune microenvironment (TIME) in NPC. Natural killer (NK) cells, as part of the innate immune system, play a crucial role in responding to viral infections and malignant cell transformations. Notably, NK cells possess a unique ability to target tumor cells independent of major histocompatibility complex class I (MHC I) expression. This means that MHC I-deficient tumor cells, which can escape from effective T cell attack, are susceptible to NK-cell-mediated killing. The activation of NK cells is determined by the signals generated through inhibitory and activating receptors expressed on their surface. Understanding the role of NK cells in the complex TIME of EBV+ NPC is of utmost importance. In this review, we provide a comprehensive summary of the current understanding of NK cells in NPC, focusing on their subpopulations, interactions, and cytotoxicity within the TIME. Moreover, we discuss the potential translational therapeutic applications of NK cells in NPC. This review aims to enhance our knowledge of the role of NK cells in NPC and provide valuable insights for future investigations.

The central role of natural killer cells in mediating acute myocarditis after mRNA COVID-19 vaccination

Vaccine-related acute myocarditis is recognized as a rare and specific vaccine complication following mRNA-based COVID-19 vaccinations. The precise mechanisms remain unclear. We hypothesized that natural killer (NK) cells play a central role in its pathogenesis. Samples from 60 adolescents with vaccine-related myocarditis were analyzed, including pro-inflammatory cytokines, cardiac troponin T, genotyping, and immunophenotyping of the corresponding activation subsets of NK cells, monocytes, and Tcells. Results were compared with samples from 10 vaccinated individuals without myocarditis and 10 healthy controls. Phenotypically, high levels of serum cytokines pivotal for NK cells, including interleukin-1β (IL-1β), interferon α2 (IFN-α2), IL-12, and IFN-γ, were observed in post-vaccination patients with myocarditis, who also had high percentage of CD57+ NK cells in blood, which in turn correlated positively with elevated levels of cardiac troponin T. Abundance of the CD57+ NK subset was particularly prominent in malesand in those after the second dose of vaccination. Genotypically, killer cell immunoglobulin-like receptor (KIR) KIR2DL5B(-)/KIR2DS3(+)/KIR2DS5(-)/KIR2DS4del(+) was a risk haplotype, in addition to single-nucleotide polymorphisms related to the NK cell-specific expression quantitative trait loci DNAM-1 and FuT11, which also correlated with cardiac troponin T levels in post-vaccination patients with myocarditis. Collectively, these data suggest that NK cell activation by mRNA COVID-19 vaccine contributed to the pathogenesis of acute myocarditis in genetically and epidemiologically vulnerable subjects. This work was funded by the Hong Kong Collaborative Research Fund (CRF) 2020/21 and the CRF Coronavirus and Novel Infectious Diseases Research Exercises (reference no. C7149-20G).

Alteration in innate immune cues assessed by analyzing peripheral blood immune system in post-covid patients

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has led to global morbidity and mortality. Some patients fully recover from COVID-19, whereas around 45% subjects suffer from various persistent symptoms (fatigue, cognitive impairment, impaired thermoregulation, skin diseases, etc.) for at least four months after SARS-CoV-2 infection regardless of disease severity. Such persistent post-infection effects are known as long-COVID, post-acute effects of COVID-19, or post-COVID state. SARS-CoV-2 infection is accompanied by damage to the innate immune system. Considering the role of natural killer cells and the activation of the complement system in COVID-19 as well as the regulatory properties related to CD46 and its potential involvement in cell virus entry, we found necessary to study immune system parameters associated with impairment of these innate immune cues on various leukocyte subpopulations in post-COVID patients. We studied 92 immune system parameters, including: pan-leukocyte markers for gated lymphocytes, phenotyping of T cells, T-helper inducers, cytotoxic T-lymphocytes, NK- and TNK-cells, T-regulatory cells/suppressors, B-lymphocytes, including B-memory cells, activated helpers, early activation of lymphocytes, activated T-lymphocytes, and late lymphocyte activation markers. Levels of total IgM, IgG, IgA, specific IgM, IgG to coronavirus COVID-19, C1-inhibitor, C3a, and C5a complement components were measured by enzyme immunoassay using Multiscan FC Thermoscientific enzyme immunoassay analyzer (China) and Vector Best reagent kits (Russia). A complete blood count was conducted to study 25 parameters: leukocyte, erythrocyte, and platelet hematopoietic lineages as well as the quantitative and qualitative composition of hematopoietic lineages. Our study results showed that in some patients, six months after suffering from COVID-19, there was a decrease in the level of NK cells (48%) and CD46+pan-leukocyte marker cells (64.5%). A decrease in NK cell levels was accompanied by increased level of total T- and B-lymphocytes, and altered platelet and erythroid hematopoietic lineages. In patients with reduced CD46 expression on T-lymphocytes, both their total count and NK cell count were significantly reduced. Our data also suggest that CD46 might be potentially involved in development of SARS-CoV-2 infection and the post-COVID state. Thus, in 50–65% of patients who have experienced SARS-CoV-2 infection, damage to the innate immune system persists after six months being accompanied by impaired erythroid and platelet hematopoietic lineages. The data obtained indicate a need for using immunocorrective therapy in such patients.

The role of Natural Killer cells in pregnancy and their potential impact on cancer prevention

Immune cells such as Natural Killer (NK) cells play a central role in immunosurveillance, preserving the physiological integrity of tissues by fighting infection and combating tumor cells, as it has the potential to release specific cytotoxic substances. Some studies suggest that a high number and/or inadequate presence/frequency of activated NK cells is involved in the Recurrent Pregnancy Loss (RPL) condition once it might trigger an immunological imbalance in women’s bodies. Our hypothesis states that a higher number of activated NK cells could be associated to lower cancer rates in women with RPL. To test this idea, we propose to evaluate abortion material, peripheral blood and uterine samples from both RPL and non-RPL women, comparing histological, cellular, and molecular features in order to identify and differentiate the immunological profile of both groups. Once established the immunological profile of both RPL and non-RPL women, an investigation of the epidemiological history of women with/without RPL can approach the possible correlation between different NK patterns and cancer reports. Scientific literature concerning this potential correlation is scarce, and we believe that a better understanding of the NK cell behavior associated to different gestational outcomes could increase our comprehension on the mechanisms underlying both cancer development and immunological aspects of pregnancy.

Defining the role of natural killer cells in COVID-19.

Natural killer (NK) cells are critical effectors of antiviral immunity. Researchers have therefore sought to characterize the NK cell response to coronavirus disease 2019 (COVID-19) and the virus that causes it, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The NK cells of patients with severe COVID-19 undergo extensive phenotypic and functional changes. For example, the NK cells from critically ill patients with COVID-19 are highly activated and exhausted, with poor cytotoxic function and cytokine production upon stimulation. The NK cell response to SARS-CoV-2 is also modulated by changes induced in virally infected cells, including the ability of a viral peptide to bind HLA-E, preventing NK cells from receiving inhibitory signals, and the downregulation of major histocompatibility complex class I and ligands for the activating receptor NKG2D. These changes have important implications for the ability of infected cells to escape NK cell killing. The implications of these findings for antibody-dependent NK cell activity in COVID-19 are also reviewed. Despite these advances in the understanding of the NK cell response to SARS-CoV-2, there remain critical gaps in our current understanding and a wealth of avenues for future research on this topic.

Understanding the link between immunosuppressant and natural killer cell in the progression of autism: The role of natural killer cell and mammalian target of rapamycin in autistic brain

Natural killer cell plays a major role in the pathogenesis of neurodevelopmental disorder including autism spectrum disorder (ASD). ASD is a neurodevelopmental disorder that is associated with symptoms that reduce the quality of life of affected individuals such as social interaction deficit, cognitive impairment, intellectual disabilities, restricted, and repetitive behavioral patterns. This disorder begins in early childhood and continues throughout adulthood. ASD pathogenesis is associated with alteration in natural killer (NK) cells as well as mammalian target of rapamycin signaling functioning that leads to altered physiological processes during development. Here, we review literature highlighting the role of immunosuppressants especially rapamycin and azathioprine and their impact on treating the neurodevelopmental disorder and mechanism by which these drugs may act to ameliorate the autistic symptoms. Furthermore, this review discusses reports highlighting the role of NK cells and familial adenomatous polyposis gene in the etiology of ASD. This review suggests that further investigative work on these drugs could be vital in the management of ASD.

The Important Roles of Natural Killer Cells in Liver Fibrosis.

Liver fibrosis accompanies the development of various chronic liver diseases and promotes their progression. It is characterized by the abnormal accumulation of extracellular matrix proteins (ECM) and impaired ECM degradation. Activated hepatic stellate cells (HSCs) are the major cellular source of ECM-producing myofibroblasts. If liver fibrosis is uncontrolled, it may lead to cirrhosis and even liver cancer, primarily hepatocellular carcinoma (HCC). Natural killer (NK) cells are a key component of innate immunity and have miscellaneous roles in liver health and disease. Accumulating evidence shows that NK cells play dual roles in the development and progression of liver fibrosis, including profibrotic and anti-fibrotic functions. Regulating NK cells can suppress the activation of HSCs and improve their cytotoxicity against activated HSCs or myofibroblasts to reverse liver fibrosis. Cells such as regulatory T cells (Tregs) and molecules such as prostaglandin E receptor 3 (EP3) can regulate the cytotoxic function of NK cells. In addition, treatments such as alcohol dehydrogenase 3 (ADH3) inhibitors, microRNAs, natural killer group 2, member D (NKG2D) activators, and natural products can enhance NK cell function to inhibit liver fibrosis. In this review, we summarized the cellular and molecular factors that affect the interaction of NK cells with HSCs, as well as the treatments that regulate NK cell function against liver fibrosis. Despite a lot of information about NK cells and their interaction with HSCs, our current knowledge is still insufficient to explain the complex crosstalk between these cells and hepatocytes, liver sinusoidal endothelial cells, Kupffer cells, B cells, and T cells, as well as thrombocytes, regarding the development and progression of liver fibrosis.

The role of natural killer cells in malaria immunity

The role of natural killer cells in malaria immunity

The central role of natural killer cells in preeclampsia.

Preeclampsia (PE) is a disease that is unique to pregnancy and affects multiple systems. It can lead to maternal and perinatal mortality. The precise etiology of PE is unclear. Patients with PE may have systemic or local immune abnormalities. A group of researchers has proposed that the immune communication between the fetus and mother is primarily moderated by natural killer (NK) cells as opposed to T cells, since NK cells are the most abundant immune cells in the uterus. This review examines the immunological roles of NK cells in the pathogenesis of PE. Our aim is to provide obstetricians with a comprehensive and updated research progress report on NK cells in PE patients. It has been reported that decidual NK (dNK) cells contribute to the process of uterine spiral artery remodeling and can modulate trophoblast invasion. Additionally, dNK cells can stimulate fetal growth and regulate delivery. It appears that the count or proportion of circulating NK cells is elevated in patients with or at risk for PE. Changes in the number or function of dNK cells may be the cause of PE. The Th1/Th2 equilibrium in PE has gradually shifted to an NK1/NK2 equilibrium based on cytokine production. An improper combination of killer cell immunoglobulin-like receptor (KIR) and human leukocyte antigen (HLA)-C may lead to insufficient activation of dNK cells, thereby causing PE. In the etiology of PE, NK cells appear to exert a central effect in both peripheral blood and the maternal-fetal interface. To maintain immune equilibrium both locally and systemically, it is necessary to take therapeutic measures directed at NK cells.

Lower percentages of natural killer cells in children with type 1 diabetes and their siblings.

One of the most common children's endocrine and autoimmune diseases in the world is type 1 diabetes mellitus (T1DM). The incidence of type 1 diabetes is constantly increasing, and according to current estimates, the number of children with T1DM in the world has exceeded 542,000. There are 3 main components emphasized in the pathogenesis: genetic and environmental factors, and the patient's immune system. Many publications have confirmed the role of natural killer cells (NK) in the pathogenesis of type 1 diabetes and other autoimmune diseases. The aim of the study was to evaluate the population of NK cells and pancreatic β cell autoantibodies in a group of children with T1DM and their healthy siblings in comparison with children from families with no history of autoimmune diseases. The research included 76 children with T1DM, 101 children from the sibling group, and 30 children from the control group. Peripheral blood was analysed on a FACSCalibur flow cytometer (Becton Dickinson) to evaluate the NK cell population. The results were presented as the percentage of NK cells among lymphocytes. Statistical analysis was performed using STATIS-TICA 10 PL software. The mean percentage of NK cells in children with T1D (10.59 ±5.37) and in the sibling group (11.93 ±5.62) was statistically reduced in comparison to the control group (14.89 ±7.78) in sequence (Student's t -test: t = -3.24; df = 103; p = 0.002) (Stu-dent's t -test: t = -2.30; df = 128; p = 0.02). There was no statistically significant difference in the percentage of NK cells be-tween the group of children with T1DM and their siblings (Student's t -test: t = -1.59; df = 173; p = 0.11). In the group of sib-lings, the younger the child, the lower the reported percentage of NK cells. This relationship was statistically significant (test for the Pearson correlation coefficient t = 3.41; p = 0.0009; r = 0.33). In the group of children with type 1 diabetes, a similar relationship was not found. The concentration of anti-IA2 and anti-Znt8 antibodies was statistically significantly higher in the sibling group compared to the control group (anti-IA2 p = 0.0000001; anti-ZnT8 p = 0.00001), and the concentration of anti-GAD antibodies was comparable in both groups. In the group of children with type 1 diabetes, a positive correlation was demonstrated between the reduced percentage of NK cells and the coexistence of anti-GAD and anti-ZnT8 antibodies (Mann-Whitney U test Z = -2.02; p = 0.04). There was no similar relationship in the group of siblings. The reduced percentage of NK cells in children with T1DM and in their siblings compared to the control group suggests the role of NK cells in the pathogenesis of T1DM. Genetic predisposition and dysfunction of NK cells probably underlie the pathogenesis of T1DM.

Unraveling the role of natural killer cells in leishmaniasis.

NK cells are known as frontline responders that are efficient in combating several maladies as well as leishmaniasis caused by Leishmania spp. As such they are being investigated to be used for adoptive transfer therapy and vaccine. In spite of the lack of antigen-specific receptors at their surface, NK cells can selectively recognize pathogens, accomplished by the activation of the receptors on the NK cell surface and also as the result of their effector functions. Activation of NK cells can occur through interaction between TLR-2 expressed on NK cells and. LPG of Leishmania parasites. In addition, NK cell activation can occur by cytokines (e.g., IFN-γ and IL-12) that also lead to producing cytokines and chemokines and lysis of target cells. This review summarizes several evidences that support NK cells activation for controlling leishmaniasis and the potentially lucrative roles of NK cells during leishmaniasis. Furthermore, we discuss strategies of Leishmania parasites in inhibiting NK cell functions. Leishmania LPG can utilizes TLR2 to evade host-immune responses. Also, Leishmania GP63 can directly binds to NK cells and modulates NK cell phenotype. Finally, this review analyzes the potentialities to harness NK cells effectiveness in therapy regimens and vaccinations.

Natural Killer Cells Are Key Host Immune Effector Cells Affecting Survival in Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation.

The infusion of autograft immune effector cells directly impacts the clinical outcomes of patients treated with autologous peripheral blood hematopoietic stem cell transplantation, suggesting the possibility of an autologous graft-versus tumor cells. Furthermore, the early recovery of immune effector cells also affects survival post-autologous peripheral blood hematopoietic stem cell transplantation. Natural killer cells are among the immune effector cells reported to be collected, infused, and recovered early post-autologous peripheral blood hematopoietic stem cell transplantation. In this review, I attempt to give an update on the role of natural killer cells regarding improving survival outcomes on patients treated with autologous peripheral blood hematopoietic stem cell transplantation.

Characteristics and Potential Roles of Natural Killer Cells During SARS-CoV-2 Infection

Abstract The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a tremendous burden on public health and world economies. An efficient host immune response to acute SARS-CoV-2 infection requires rapid and early activation of the innate immune system. Natural killer (NK) cells represent a critical component of the innate immunity. Here, the appearance of CD56-CD16+ NK cells and unconventional CD56dim CD16neg NK cells during the course of SARS-CoV-2 infection, and the phenotype and effector functions of NK cells during SARS-CoV-2 infection were summarized. The involvement of the dysregulated NK cells in the immunopathogenesis of the coronavirus disease 2019 (COVID-19) and clinical trials of adoptive NK cell–based therapies against COVID-19 were also discussed.

Features of the State of Cellular and Humoral Markers of the Immune System in Breast Cancer among Women in Aktobe Region

Features of the State of Cellular and Humoral Markers of the Immune System in Breast Cancer among Women in Aktobe Region

Non-Classical HLA Determinants of the Clinical Response after Autologous Stem Cell Transplantation for Systemic Sclerosis.

Systemic Sclerosis (SSc) is a chronic autoimmune disease with high morbidity and mortality. Autologous Hematopoietic Stem Cell Transplantation (AHSCT) is the best therapeutic option for rapidly progressive SSc, allowing increased survival with regression of skin and lung fibrosis. The immune determinants of the clinical response after AHSCT have yet to be well characterized. In particular, the pivotal role of the Human Leukocyte Antigen (HLA) system is not well understood, including the role of non-classical immuno-modulatory HLA-E and HLA-G molecules in developing tolerance and the role of Natural Killer cells (NK) in the immunomodulation processes. We retrospectively tested whether the genetic and/or circulating expression of the non-classical HLA-E and HLA-G loci, as well as the imputed classical HLA determinants of HLA-E expression, influence the observed clinical response to AHSCT at 12- and 24-month follow-up. In a phenotypically well-defined sample of 46 SSc patients classified as clinical responders or non-responders, we performed HLA genotyping using next-generation sequencing and circulating levels of HLA-G and quantified HLA-E soluble isoforms by ELISA. The -21HLA-B leader peptide dimorphism and the differential expression level of HLA-A and HLA-C alleles were imputed. We observed a strong trend towards better clinical response in HLA-E*01:03 or HLA-G 14bp Del allele carriers, which are known to be associated with high expression of the corresponding molecules. At 12-month post-AHSCT follow-up, higher circulating levels of soluble HLA-E were associated with higher values of modified Rodnan Skin Score (mRSS) (p = 0.0275), a proxy of disease severity. In the non-responder group, the majority of patients carried a double dose of the HLA-B Threonine leader peptide, suggesting a non-efficient inhibitory effect of the HLA-E molecules. We did not find any correlation between the soluble HLA-G levels and the observed clinical response after AHSCT. High imputed expression levels of HLA-C alleles, reflecting more efficient NK cell inhibition, correlated with low values of the mRSS 3 months after AHSCT (p = 0.0087). This first pilot analysis of HLA-E and HLA-G immuno-modulatory molecules suggests that efficient inhibition of NK cells contributes to clinical response after AHSCT for SSc. Further studies are warranted in larger patient cohorts to confirm our results.

Roles of natural killer cells in immunity to cancer, and applications to immunotherapy.

Great strides have been made in recent years towards understanding the roles of natural killer (NK) cells in immunity to tumours and viruses. NK cells are cytotoxic innate lymphoid cells that produce inflammatory cytokines and chemokines. By lysing transformed or infected cells, they limit tumour growth and viral infections. Whereas T cells recognize peptides presented by MHC molecules, NK cells display receptors that recognize stress-induced autologous proteins on cancer cells. At the same time, their functional activity is inhibited by MHC molecules displayed on such cells. The enormous potential of NK cells for immunotherapy for cancer is illustrated by their broad recognition of stressed cells regardless of neoantigen presentation, and enhanced activity against tumours that have lost expression of MHC class I owing to acquired resistance mechanisms. As a result, many efforts are under way to mobilize endogenous NK cells with therapeutics, or to provide populations of ex vivo-expanded NK cells as a cellular therapy, in some cases by equipping the NK cells with chimeric antigen receptors. Here we consider the key features that underlie why NK cells are emerging as important new additions to the cancer therapeutic arsenal.