scholarly journals Ovarian Stimulation Affects the Population of Mouse Uterine NK Cells at Early Pregnancy

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Parvin Dorfeshan ◽  
Mojdeh Salehnia ◽  
Seyed Mohammad Moazzeni
Keyword(s):  
Nk Cells ◽  
Ovarian Stimulation ◽  
Nk Cell ◽  
Embryo Implantation ◽  
Control Group ◽  
Tissue Samples ◽  
Serum Gonadotropin ◽  
Human Chorionic Gonadotropin Hormone ◽  
Uterine Nk Cells ◽  
Fertile Male

The aim of this study was to determine the influence of ovarian stimulation on endometrial mouse NK cell population. For superovulation, the female adult NMRI mice were injected i.p. with 10 IU of the pregnant mare serum gonadotropin followed 48 h later by an i.p. injection of 10 IU human chorionic gonadotropin hormone. Ovarian stimulated and nonstimulated mice were mated with fertile male. The presence of vaginal plug proved natural pregnancy, and this day was considered as day one of pregnancy. Tissue samples were prepared from the uterine horn and spleen of both groups of study on 7th day of pregnancy. Serum estradiol-17βand progesterone were measured at the same time. The tissue cryosections were prepared and double stained for CD 161 and CD3 markers, and NK cells population was analyzed. Relative frequency of NK cells was significantly lower in stroma and myometrium in hyperstimulated mice compared with the control group. However, no difference was seen in percentage of NK cells in spleen. The ovarian stimulation influences the proportion of uterine NK cells and may affect the embryo implantation.

scholarly journals A Brief Analysis of Tissue-Resident NK Cells in Pregnancy and Endometrial Diseases: The Importance of Pharmacologic Modulation

Immuno ◽  
2021 ◽  
Vol 1 (3) ◽  
pp. 174-193
Author(s):  
Jenny Valentina Garmendia ◽  
Juan Bautista De Sanctis
Keyword(s):  
Nk Cells ◽  
Nk Cell ◽  
Embryo Implantation ◽  
Inflammatory Cells ◽  
Cell Physiology ◽  
Therapeutic Approaches ◽  
Pharmacological Modulation ◽  
New Therapeutic Approaches ◽  
Pharmacologic Modulation ◽  
Inflammatory Burden

NK cells are lymphocytes involved in the innate and adaptative immune response. These cells are located in peripheral blood and tissues with ample functions, from immune vigilant to tolerogenic reactions. In the endometrium, NK cell populations vary depending on age, hormones, and inflammation. When pregnancy occurs, tissue-resident NK cells and conventional NK cells are recruited to protect the fetus, a tolerogenic response. On the contrary, in the inflamed endometrium, various inflammatory cells down-regulate NK tolerance and impair embryo implantation. Therefore, NK cells’ pharmacological modulation is difficult to achieve. Several strategies have been used, from progesterone, lipid emulsions to steroids; the success has not been as expected. However, new therapeutic approaches have been proposed to decrease the endometrial inflammatory burden and increase pregnancy success based on understanding NK cell physiology.

Abstract WP319: miRNA Screening of Natural Killer Cell Identifies miR-1224 as a Post-Transcriptional Regulator of NK Cell Function After Ischemic Stroke

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Yan Feng ◽  
Hui Zhao ◽  
Fu-Dong Shi ◽  
Weina Jin
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Nk Cells ◽  
Expression Profile ◽  
Mirna Expression ◽  
Cell Function ◽  
Nk Cell ◽  
Killer Cell ◽  
Mirna Expression Profile ◽  
Control Group

Objectives: To screen miRNA profile of peripheral NK cells in ischemic stroke mouse model and investigate a most promising candidate (miR-1224) for post-transcriptional regulation of NK cell function after ischemic stroke. Methods: Mice were subjected to a 60 min focal cerebral ischemia produced by transient intraluminal occlusion of MCAO. For NK cell isolation, cell suspensions from the spleens after reperfusion were enriched for NK cells using magnetic-bead sorting system after staining with anti-NK1.1 microbeads. The nCounter Mouse miRNA array was used to analyze miRNA expression profile in splenic NK cells over the time course of experimental ischemic stroke. Based on the miRNA data, we further in vitro modulated miR-1224 in NK cells using mimics or inhibitor, then injected i.v into Rag2-/-γc-/- recipient mice. Neurological function score was compared and spontaneous infection was assessed by pulmonary bacteria colony culture, and changes in potential signaling pathway (SP1/TNF-α) were verified by rt-PCR and western blot. Results: Through miRNA expression profile analysis, we have identified significant changes at each time point in peripheral NK cells after cerebral ischemia. Among all screened miRNA, miR-1224 remarkably increased in MCAO group, which was verified by PCR. Then isolated NK cells treated with mimics or inhibitors, were transferred to Rag2-/-γc-/- recipient mice. Compared with WT mice, Rag2-/-γc-/- mice with miR-1224 inhibitor exhibited increased NK cell number, enhanced NK cell activation/cytotoxicity feature, as well as better neurological behaviors and reduced pulmonary infection after MCAO. Moreover, compared with the control group, NK cells with miR-1224 inhibitor showed significantly increased SP1 gene and protein phosphorylation. As SP1 gene is one of the potential targets of miR-1224, this study suggests that miR-1224 may regulate NK cell function after MCAO, which is associated with SP1 pathway. Conclusion: The miRNA profiling of splenic NK cells provided insight into the functional mechanism and signaling pathways underlying the distinct organ-specific NK cell properties, which will contribute to the better understanding of NK cell mediated immune-response in relation to different stages of stroke.

Acute Exercise Increases the Expression of KIR2DS4 by Promoter Demethylation in NK Cells

2018 ◽  
Vol 40 (01) ◽  
pp. 62-70 ◽  
Author(s):  
Alexander Schenk ◽  
Walter Pulverer ◽  
Christine Koliamitra ◽  
Claus Bauer ◽  
Suzana Ilic ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Nk Cells ◽  
Promoter Methylation ◽  
Acute Exercise ◽  
Nk Cell ◽  
Epigenetic Modifications ◽  
Control Group ◽  
Chronic Exercise ◽  
Positive Effects

AbstractPositive effects of exercise on cancer prevention and progression have been proposed to be mediated by stimulating natural killer (NK) cells. Because NK cell receptors are regulated by epigenetic modifications, we investigated whether acute aerobic exercise and training change promoter DNA methylation and gene expression of the activating KIR2DS4 and the inhibiting KIR3DL1 gene. Sixteen healthy women (50–60 years) performed a graded exercise test (GXT) and were randomized into either a passive control group or an intervention group performing a four-week endurance exercise intervention. Blood samples (pre-, post-GXT and post-training) were used for isolation of DNA/RNA of NK cells to assess DNA promoter methylation by targeted deep-amplicon sequencing and gene expression by qRT-PCR. Potential changes in NK cell subsets were determined by flow cytometry. Acute and chronic exercise did not provoke significant alterations of NK cell proportions. Promoter methylation decreased and gene expression increased for KIR2DS4 after acute exercise. A high gene expression correlated with a low methylation of CpGs that were altered by acute exercise. Chronic exercise resulted in a minor decrease of DNA methylation and did not alter gene expression. Acute exercise provokes epigenetic modifications, affecting the balance between the activating KIR2DS4 and the inhibiting KIR3DL1, with potential benefits on NK cell function.

scholarly journals The phenotype of NK-cells in the dynamics of the post-operative period in patients with peritonitis in depending on the outcome of the disease

2019 ◽  
Vol 9 (3-4) ◽  
pp. 539-548
Author(s):  
A. A. Savchenko ◽  
A. G. Borisov ◽  
I. V. Kudryavcev ◽  
V. D. Belenjuk
Keyword(s):  
Nk Cells ◽  
Postoperative Period ◽  
Peripheral Blood ◽  
Nk Cell ◽  
Favorable Outcome ◽  
Control Group ◽  
Preoperative Period ◽  
Surface Receptors ◽  
Post Surgery ◽  
Purulent Peritonitis

Our study was aimed at investigating dynamic phenotype pattern of peripheral blood NK cells in patients with widespread purulent peritonitis (WPP) during postoperative period depending on disease outcome. A total of 48 patients aged 30–63 with acute surgical diseases and abdominal injuries complicated by WPP were examined. Blood sampling was performed before surgery (preoperative period) as well as on day 7, 14 and 21 during postoperative period. 40 apparently healthy age-matched subjects were included in control group. Peripheral blood NK cell phenotyping was performed by using flow cytometry with directly immunofluorescently tagged antibodies. Mean fluorescence intensity was measured to estimate expression levels of NK cell surface receptors was measured. It was found that in patients with a favorable WPP outcome during preoperative period the percentage of mature NK cells was decreased that was restored by the end of the postoperative period (21 days post-surgery) due to elevated mature, cytotoxic and cytokine-producing NK cell subsets. In addition, percentage of CD11b-positive NK cell subsets was increased upon favorable outcome by the end of postoperative period as well as frequency of CD57-positive NK cells relative to the preoperative period. However, frequency of mature NK cells with unfavorable WPP outcome vs. control vs. favorable outcome was decreased during preoperative and entire postoperative period. Moreover, amount of cytotoxic NK cells was elevated during examination period upon unfavorable WPP outcome. Further, percentage of mature CD11b-positive NK cells in this patient cohort was decreased during preoperative period and post-surgery. Percentage of CD57-positive NK cells was decreased during entire postoperative period in patients with unfavorable vs. favorable outcome vs. control group. At the same time, patients with unfavorable outcome of this infectious-inflammatory disease were shown to display upregulated expression of CD28 and CD57 markers on NK cells. such features identified in phenotype of peripheral blood NK cells in patients with unfavorable WPP outcome reflect abnormal mechanisms in NK cell maturation and migration, which, in turn, determines disturbance in events regulating acute inflammatory reaction in WPP. 

scholarly journals Suppression of Natural Killer Cell Cytotoxicity in Postpartum Women

2013 ◽  
Vol 16 (3) ◽  
pp. 320-326 ◽  
Author(s):  
Maureen W. Groer ◽  
Nagwa El-Badri ◽  
Julie Djeu ◽  
S. Nicole Williams ◽  
Bradley Kane ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Postpartum Period ◽  
Nk Cell ◽  
Killer Cell ◽  
Control Group ◽  
Postpartum Women ◽  
Cell Cytotoxicity ◽  
Natural Killer Cell Cytotoxicity ◽  
Nk Cytotoxicity

Little is known about the recovery of the immune system from normal pregnancy and whether the postpartum period is a uniquely adapted immune state. This report extends previous observations from our group of decreased natural killer (NK) cell cytotoxicity in the postpartum period. NK cytotoxicity was measured from 1 week through 9 months postpartum. In addition, NK cytotoxicity was assayed in the presence or absence of pooled plasmas collected from either postpartum or nonpostpartum women. Samples of cells were stained for inhibitory receptors and analyzed by flow cytometry. NK cytotoxicity remained decreased in postpartum women compared to controls through the first 6 postpartum months, returned to normal levels by 9 months, and remained normal at 12 months. NK cytotoxicity during the first 6 months was further inhibited by the addition of pooled plasma to NK cultures from postpartum women, but the addition of pooled plasma from the control group did not affect that group’s NK cultures. There were differences in inhibitory receptor staining between the two groups, with decreased CD158a and CD158b and increased NKG2A expression on postpartum NK cells during the first 3 postpartum months. These data suggest that NK cytotoxicity postpartum inhibition lasts 6 months and is influenced by unidentified postpartum plasma components. The effect may also involve receptors on NK cells.

scholarly journals Analysis of cell-mediated immunity in people with long Covid.

2021 ◽  
Author(s):  
Nerea Montes ◽  
Èlia Domènech ◽  
Silvia Guerrero ◽  
B&aacuterbara Oliv&aacuten-Bl&aacutezquez ◽  
Rosa Magallón-Botalla
Keyword(s):  
Nk Cells ◽  
Immune Cell ◽  
Nk Cell ◽  
Humoral Response ◽  
Cross Sectional Study ◽  
Control Group ◽  
Cell Mediated Immunity ◽  
Specific Cell ◽  
Cross Sectional ◽  
Persistent Symptoms

Introduction: The objective of this study is to analyse the specific immune response against SARS-CoV-2 in those affected by Long Covid (LC), attributable to T cells (cell-mediated immunity) and to carry out a parallel analysis of the humoral response and lymphocyte typing. Methodology: Descriptive cross-sectional study of 74 patients with LC for at least 4 months since diagnosis. The collected data were: information on the COVID-19 episode and the persistent symptoms, medical history and a specific cell-mediated immunity to SARS-CoV-2 through flow cytometry, assessing the release of interferon-gamma (IFN-Ɣ) by T4 lymphocytes, T8 lymphocytes and NK cells. Descriptive and comparative analyses were carried out. Results: Patients with LC had negative serology for Covid-19 in 89% of cases but 96% showed specific cellular immunity to SARS-CoV-2 an average of 9.5 months after infection: 89% of this response corresponded to T8 lymphocytes, 58% to NK cells, and 51% to T4 lymphocyte (20% negligibly positive). Most of them had altered immune cell typing and we found that T4 lymphocyte counts were low in 34% of cases and NK cell high in 64%. Macrophage populations were detected in the peripheral blood of 7% of them. Patients displayed a higher percentage of illnesses related to ″abnormal″ immune responses, either preceding SARS-CoV-2 infection (43%) or following it in 23% of cases. Conclusion: The immune system appears to have an important involvement in the development of LC and viral persistence could be the cause or consequence of it. Further analysis with a control group should be performed.

scholarly journals Modulation of the human immune status by spinal thermal massage: a non-randomized controlled study

2021 ◽  
Keyword(s):  
Quality Of Life ◽  
Nk Cells ◽  
Nk Cell ◽  
Controlled Trial ◽  
Controlled Study ◽  
Control Group ◽  
Randomized Controlled ◽  
Significant Difference ◽  
Experimental Group

Thermal and massage therapies have long been used to control pain. Although spinal thermal massage (STM) has been used worldwide, its effectiveness has not been proven in a controlled clinical study. We here conducted a non-randomized controlled trial to assess the pain-relieving and immunomodulatory effects of STM in old-aged patients experiencing pain or disability. The experimental group was treated with STM five times a week for 8 weeks and rehabilitative regular care (RRC). The control group was treated with only RRC. Pain and immunological parameters were tested before treatment and after 4 and 8 weeks of treatment. The scores of three pain parameters were lowered by STM, and the differences between the groups were statistically significant at the two time points (p < 0.01). Quality of life determined using the 3-level EuroQol five-dimensional questionnaire scores was significantly higher in patients in the experimental group than those in the control group. Effect sizes (ES) were in the range of medium to large in the pain-related measures (0.54–1.22). The total leukocyte counts and the proportions of lymphocytes and subsets were not significantly different between the groups, whereas the proportions of monocytes and natural killer (NK) cells were higher in the experimental group than in the control group after 8 weeks (p < 0.05). The production of interleukin (IL)-4 and interferon γ in T cells was not significantly different between the groups, whereas the production of IL-2 was high in the control group. However, there was a significant increase in IFN-γ production by NK cells in the experimental group (at 4 weeks, p < 0.05). ES were medium in the immunological measures (0.53–0.68). No significant difference was observed in the production of proinflammatory cytokines, IL-1β, tumor necrosis factor α, or IL-6 between the groups. In conclusion, STM treatment has a positive effect on subjective pain and quality of life. It also enhanced NK cell proportion and activity, suggesting that STM may be beneficial in the prevention of viral diseases and cancer in old-aged people.

Effect of eccentric exercise on natural killer cell activity

1995 ◽  
Vol 78 (4) ◽  
pp. 1442-1446 ◽  
Author(s):  
J. Palmo ◽  
S. Asp ◽  
J. R. Daugaard ◽  
E. A. Richter ◽  
M. Klokker ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Eccentric Exercise ◽  
Nk Cell ◽  
Killer Cell ◽  
Cell Activity ◽  
Control Group ◽  
Systemic Effects ◽  
Nk Cell Activity ◽  
Blood Samples

The effect of eccentric one-legged exercise on natural killer (NK) cell activity was studied in eight healthy males. To distinguish between local and systemic effects, blood samples were collected from veins in the exercising leg and resting arm. However, the results did not significantly differ between the leg and arm. To eliminate diurnal variations, the results were compared with a control group that did not exercise but had blood samples collected at the same time points. In the exercising group, plasma creatine kinase increased progressively during and up to 4 days after exercise. The percentage of CD16+ NK cells increased during exercise, which was paralleled by an increase in the NK cell activity per fixed number of blood mononuclear cells. The NK cell activity on a per NK cell basis did not change. The percentage of CD3+, CD4+, CD8+, CD19+, and CD14+ cells did not change significantly during exercise. The present study thus showed that eccentric exercise with a relatively small muscle mass (1 quadriceps femoris muscle) causes systemic effects on NK cells. It is suggested that the increase in plasma epinephrine during eccentric exercise is responsible for the observed increase in the percentage of CD16+ cells.

75 INHIBITION OF NK CELL CYTOTOXICITY IN CLONED MINI-PIGS EXPRESSING HUMAN LEUKOCYTE ANTIGEN-G1 (HLA-G1) GENE

2007 ◽  
Vol 19 (1) ◽  
pp. 155
Author(s):  
K. W. Park ◽  
G. S. Han ◽  
K. M. Choi ◽  
S. P. Hong ◽  
J. Y. Yoo ◽  
...  
Keyword(s):  
Nk Cells ◽  
Cell Lines ◽  
Nk Cell ◽  
Control Group ◽  
Cell Cytotoxicity ◽  
Xenograft Rejection ◽  
Clonal Cell ◽  
Fetal Fibroblasts ◽  
Clonal Cell Lines ◽  
Mini Pigs

Human natural killer (NK) cell-mediated response plays an important role in xenograft rejection. In the case of pig-to-human xenotransplantation, it has been suggested that NK cells are involved in delayed-type rejection, which is characterized by pig endothelial cell (pEC) activation, direct lysis, and secretion of proinflammatory cytokines. NK cell activation can be a direct barrier to the potential use of pig organs for human xenograft transplantation. Therefore, it is important to suppress the NK cell activity on pig-to-human xenografts. Expression of HLA-G1 (non-classical major histocompatibility complex class I molecules) inhibits the cytotoxic activity of NK cells and has been proposed as a potential solution to overcome NK cell-mediated xenogeneic cytotoxicity in pEC. In this study, we transfected the HLA-G1 gene into mini-pig fetal fibroblasts to produce 2 HLA-G1 clonal cell lines. These cell lines were used to produce cloned HLA-G1 transgenic mini-pigs by nuclear transfer (NT). The presence of the HLA-G1 gene in transgenic mini-pigs was confirmed by PCR. The expression of HLA-G1 was detected by flow cytometry-immunohistochemistry assay. Mini-pig fibroblasts derived from a 35-day-old cloned fetus also showed characteristics similar to those of HLA-G1 clonal cell lines. The expressed HLA-G1 significantly suppressed NK-mediated cell lysis, and the rate of NK 92MI cell cytotoxicity was reduced as compared to the control group (HLA-G1: 46.7 � 4.5%; control: 4.6 � 13.3%; P &lt; 0.05). In conclusion, transgenic cloned mini-pigs expressing HLA-G1 were produced by NT for the first time. It is expected that these mini-pigs could be used to overcome the NK cell-mediated rejection in xenotransplantation.

Adoptive transfer of NK cells in combination with chemotherapy to improve outcomes of patients with locally advanced colon carcinoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15038-e15038 ◽  
Author(s):  
Lingyu Li ◽  
Jiuwei Cui ◽  
Chang Wang ◽  
Yizhuo Wang ◽  
Chao Niu ◽  
...  
Keyword(s):  
Cohort Study ◽  
Cell Therapy ◽  
Nk Cells ◽  
Nk Cell ◽  
Locally Advanced ◽  
Cell Group ◽  
Control Group ◽  
Poorly Differentiated ◽  
Local Advanced ◽  
Nk Cell Therapy

e15038 Background: The prognosis of advanced colon cancer (CC) patients remains disappointing, partly due to their greater proportion of CC-initiating cells (CICs), which is responsible for cancer drug-resistance and immune escape. Immunotherapies by harnessing the immune system to eliminate tumors have attracted broad attention. This study was to detect whether chemotherapy could enhance cytotoxicity of natural killer (NK) cells to CC cells (CCs), especially for CICs in vitro, and further evaluate the efficacy and safety of NK-cell therapy combined with chemotherapy in patients with local advanced CC. Methods: We observed that cytotoxicity of NK cells to CCs and CICs pretreated with 5-Fu or oxaliplatin. Then, an open-label pilot cohort study was conducted with local advanced CC patients who had received surgical excision. 60 patients elected to receive either NK-cell therapy combined with chemotherapy (NK-cell group, 27 patients) or pure chemotherapy (control group, 33 patients). Progression-free survival (PFS), overall survival (OS) and adverse effects were investigated. Results: Chemotherapy sensitized CCs and CICs to NK cell lysis through upregulation of their NK cell activating ligands and reducing inhibitory ligands. Poorly differentiated CCs were more susceptible to NK-cell than well-differentiated CCs, and CICs were more easily to be killed by NK cell than their differentiated CCs. In the cohort study, the 5-year PFS and OS rates in the NK-cell group were significantly higher than those in the control group (51.1% vs. 34.9%, p= 0.043; 73% vs. 51.3%, p= 0.038, respectively).Among patients with poorly differentiated carcinomas or low expression of HLA-1, median PFS in the NK-cell group vs. the control group was 23.5 vs. 11.5 months ( p= 0.047), and median OS was 30 vs. 15 months ( p= 0.043), respectively. No significant adverse reaction was found during NK-cell therapy. Conclusions: NK-cell therapy in combination with chemotherapy in locally advanced CC prevented recurrence and prolonged survival with acceptable adverse effects, especially for poorly differentiated carcinomas.

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