Natural killers

Plants and natural molecules are generally consumed not in raw state but after different processing conditions (heating, mechanical agitation or cooking). The understanding of the chemistry and biological outcome of thermal treatment is still scarce. In the current study, Eriodictyol, a natural flavanone, has undergone heat treatment, generating hence three different products ((3-(3,4-dihydroxyphenyl)-3-hydroxypropanoic acid, (3-(3,4-dihydroxyphenyl) propanal) and an unidentified component). The consequences of aforementioned treatment on the immunomodulatory behavior of resulted molecules were evaluated...

BACKGROUND: The ability to predict which recipients will successfully complete their posttransplant clinical course, is crucial for liver transplant (LT) programs. The assessment of natural killer (NK) cell subset determined by flow cytometry from a monocentric series of consecutive liver perfusates (LPs) could help identify risk factors portending adverse LT outcomes. METHODS: LPs were collected during the back-table surgical time after the procurement procedures for donors after brain death (DBDs)...

γδ T cell-based immunotherapy for osteosarcoma (OS) has shown limited success thus far. DNA-demethylating agents not only induce tumor cell death but also have an immunomodulatory function. In this study, we have assessed the potential benefit of combining decitabine (DAC, a DNA demethylation drug) and γδ T cells for OS immunotherapy. DAC increased the expression of natural killer group 2D (NKG2D) ligands (NKG2DLs), including major histocompatibility complex class I-related chains B (MICB) and UL16-binding protein 1 (ULBP1), on the OS cell surface, making the cells more sensitive to recognition and destruction by cytotoxic γδ T cells...

Current medicine and medical science puts great effort into elucidating the basis of chronicity and finding appropriate treatments for inflammatory diseases; however, the mechanisms driving aberrant immune responses are mostly unknown and deserve further study. Of particular interest is the identification of checkpoints that regulate the function and differentiation of pro-inflammatory cells during pathogenesis, along with means of their modulation for therapeutic purposes. Natural killer group 2, member D (NKG2D) is a potent activator of the immune system, known as a sensor for "induced-self" ligands, i...

Mesenchymal stromal cells (MSC) present in the tumor microenvironment [usually named tumor-associated fibroblasts (TAF)] can exert immunosuppressive effects on T and natural killer (NK) lymphocytes, favoring tumor immune escape. We have analyzed this mechanism in colorectal carcinoma (CRC) and found that co-culture of NK cells with TAF can prevent the IL-2-mediated NKG2D upregulation. This leads to the impairment of NKG2D-mediated recognition of CRC cells, sparing the NK cell activation through DNAM1 or FcγRIIIA (CD16)...

Haploidentical stem cell transplantation with T cell-replete grafts and post-transplant cyclophosphamide (PTCy) is increasingly used with encouraging outcome. Natural killer (NK) cell alloreactivity, predicted by missing killer cell immunoglobulin-like receptor (KIR) ligands in the recipient that are present in their donor improves outcome of T cell-depleted haploidentical transplants. We explored the role of KIR ligand mismatching in 444 acute leukemia patients after T cell-replete transplants with PTCy. Thirty-seven percent of all patients had KIR ligand mismatching...

Researchers have discovered how the gut microbiome affects tumor development in the mouse liver. By treating mice with antibiotics, they showed that depleting gut commensal bacteria enhances certain primary bile acids in the liver. This causes natural killer T cells to accumulate there, where they protect against tumors. A trial to determine whether this mechanism also operates in humans is being planned.

BACKGROUND: Obstructive jaundice (OJ) patients with cholangitis are prone to sepsis; however, the underlying mechanisms are still not clear and need to be clarified. METHODS: Analyzing all available published data related to the title of this article. RESULTS: OJ leads to absence of gut luminal bile and accumulation of hepatic and circulating bile acids. Absence of gut luminal bile deprives the gut from its antiinflammatory, endotoxin-binding, bacteriostatic, mucosal-trophic, epithelial tight-junction maintaining, and gut motility-regulating effects, leading to gut bacterial overgrowth, mucosal atrophy, mucosal tight-junction loss, and gut motility dysfunction...

The inability to elicit strong and durable cellular responses is a major obstacle in the development of successful vaccines, in particular those against malaria. In this regard, the generation of novel adjuvants that will potently boost cell-mediated immunity induced by candidate vaccines is helpful. We and others have found a glycolipid, called α-galactosylceramide (α-GalCer), which could be presented on CD1d expressed by antigen-presenting cells (APCs) and stimulate natural killer T (NKT) cells. This triggers the activation/maturation of APCs, particularly dendritic cells (DCs)...

Natural killer (NK) cells are lymphocytes with important anti-tumour functions. Cytokine activation of NK cell glycolysis and oxidative phosphorylation (OXPHOS) are essential for robust NK cell responses. However, the mechanisms leading to this metabolic phenotype are unclear. Here we show that the transcription factor cMyc is essential for IL-2/IL-12-induced metabolic and functional responses in mice. cMyc protein levels are acutely regulated by amino acids; cMyc protein is lost rapidly when glutamine is withdrawn or when system L-amino acid transport is blocked...

Immunological memory is broadly understood as the underlying mechanism by which an organism remembers previous encounters with pathogens, aberrant cells, or self-antigens to produce a more rapid or robust secondary response upon re-encounter. This phenomenon is widely accepted as the hallmark feature of the adaptive immune system. However, work within the last decade has continuously challenged this viewpoint and opened up the idea that immunological memory extends beyond just conventional B cells and T cells...

Siglec-9 is an MHC-independent inhibitory receptor selectively expressed on CD56dim NK cells. Its role in infection diseases has not been investigated yet. Here, we studied the potential regulatory roles of NK Siglec-9 in the pathogenesis of chronic hepatitis B (CHB) infection. Flow cytometry evaluated the expression of Siglec-9 and other receptors on peripheral NK cells. Immunofluorescence staining was used to detect Siglec-9 ligands on liver biopsy tissues and cultured hepatocyte cell lines. Siglec-9 blocking assay was carried out and cytokine synthesis and CD107a degranulation was detected by flow cytometry...

Background: Previous studies have demonstrated the prognostic value of globulin (GLB), albumin (ALB), the ALB/GLB ratio (AGR), body mass index (BMI), hemoglobin (Hb), and prognostic nutritional index (PNI) in breast cancer. The underlying mechanism has been investigated by examining the impact of nutritional parameters on T cells, natural killer cells, and dendritic cells, but little is known about their effect on checkpoint molecules. Methods: Here, we investigated the correlation of mRNA expression of programmed cell death protein 1 (PD-1), cluster of differentiation 28 (CD28), cytotoxic T-lymphocyte antigen-4 (CTLA-4), and cluster of differentiation 25 (CD25) with AGR, ALB, GLB, total protein, pre-ALB, Hb, BMI, and PNI in the peripheral blood of breast cancer patients...

BACKGROUND: Pixatimod (PG545) is a novel clinical-stage immunomodulatory agent capable of inhibiting the infiltration of tumor-associated macrophages (TAMs) yet also stimulate dendritic cells (DCs), leading to activation of natural killer (NK) cells. Preclinically, pixatimod inhibits heparanase (HPSE) which may be associated with its inhibitory effect on TAMs whereas its immunostimulatory activity on DCs is through the MyD88-dependent TLR9 pathway. Pixatimod recently completed a Phase Ia monotherapy trial in advanced cancer patients...

BACKGROUND: Influenza infects tens of millions of people every year in the USA. Other than notable risk groups, such as children and the elderly, it is difficult to predict what subpopulations are at higher risk of infection. Viral challenge studies, where healthy human volunteers are inoculated with live influenza virus, provide a unique opportunity to study infection susceptibility. Biomarkers predicting influenza susceptibility would be useful for identifying risk groups and designing vaccines...

Hepatic irradiation for the treatment of hepatobiliary malignancies often indirectly damages liver tissue and promotes the development of liver fibrosis. However, little is known concerning the effects of hepatic irradiation on the liver immune system, including natural killer (NK) cells. The aim of this study was therefore to investigate how hepatic irradiation influences the functions and characteristics of liver resident NK cells. An established murine hepatic irradiation model was used to examine the specific effects of hepatic irradiation on immune cell populations and metastasis...

Background: γδ T cells are effector lymphocytes recognized as key players during chronic inflammatory processes. Mouse studies suggest a pathological role for γδ T cells in models of kidney disease. Here we evaluated γδ T cells in human native kidneys with tubulointerstitial fibrosis, the pathological hallmark of chronic kidney disease. Methods: γδ T cells were extracted from human kidney tissue and enumerated and phenotyped by multicolour flow cytometry...

Epstein-Barr virus (EBV), which is associated with B-cell proliferative disorders, also transforms T- or natural killer (NK)-lineage cells and has been connected with various T- or NK (T/NK)-cell malignancies, such as extranodal NK/T-cell lymphoma-nasal type and aggressive NK-cell leukemia. Chronic active EBV (CAEBV) disease , which occurs most often in children and young adults in East Asia, is an EBV-associated T-/NK-cell lymphoproliferative disease. Patients with CAEBV often progress to overt lymphoma or leukemia over a long-term clinical course...

CD8+ T cells are considered prototypical cells of adaptive immunity. Here, we uncovered a distinct CD8+ T cell population expressing the activating natural killer (NK) receptor NKp30 in the peripheral blood of healthy individuals. We revealed that IL-15 could de novo induce NKp30 expression in a population of CD8+ T cells and drive their differentiation toward a broad innate transcriptional landscape. The adaptor FcεRIγ was concomitantly induced and was shown to be crucial to enable NKp30 cell-surface expression and function in CD8+ T cells...

OBJECTIVE: Cellular immune status in major depression (MD) patients differs from that in somatoform disorder (SFD) patients and healthy controls (HC). It is still questionable whether the patterns of immune parameters remain stable over time. Therefore, we studied lymphocyte and monocyte cell counts and neopterin levels in peripheral blood of MD and SFD patients and HC over 12 weeks and tested for correlations between biochemical and psychometric parameters. METHODS: Thirty-nine patients with MD, 27 with SFD, and 51 HC were recruited...