Результаты поиска

Rapamycin prevents spontaneous abortion by triggering decidual stromal cell autophagy-mediated NK cell residence.

Deficiency in decidualization has been widely regarded as an important cause of spontaneous abortion. Generalized decidualization also inclu … ell; PECAM1/CD31: platelet and endothelial cell adhesion molecule 1; pNK: peripheral blood NK; PRF1/Perforin: Perforin 1; PTPRC/CD45: protein tyrosine phosphatase receptor type C; Rapa: rapamycin; rh-TNFSF14/LIGHT: recombinant human TNFSF14/LIGHT; SA: spontaneous abortion; SELE: selectin E; SELP: selectin P; SELL: selectin L; siATG5 DSCs: ATG5-silenced DSC …

[Expression and Function of MAIT Cells in Patients with Newly Diagnosed Acute Myeloid Leukemia].

OBJECTIVE: To explore the changes in number and immune function of mucosal-associated invariant T (MAIT) cells in peripheral blood of patien … . AML patients' peripheral blood MAIT cells expressed significantly higher levels of granzyme B and perforin than healthy controls (both P < 0.05), and secreted significantly lower levels of cytokines such as gamma interferon and tumor necrosis factor α than healthy controls (both P < 0.001). CONCLUSION: Compared with healthy controls, the proportion of M …

Circulating CD8 + LGALS9 + T Cell Population Exhibiting Low Cytotoxic Characteristics are Decreased in Patients with Systemic Lupus Erythematosus.

LGALS9, also known as Galectin-9 and a member of the β-galactosidase family, plays a crucial role in immune regulation. However, its express … to LGALS9 + CD8 + T cells, LGALS9-CD8 + T cells showed increased secretion of Granzyme B (GZMB) and Perforin, along with elevated expression levels of GPR56, CX3CR1, KLRD1, KLRF1, PD1, and CD29. A higher proportion of Tn (naive T cells) and TCM (central memory T cells) showed LGALS9 positivity, compared to TEM (effector memory T cells) and TEMRA (terminall …

A novel PhoP-regulated locus encoding the cytolysin ClyA and the secreted invasin TaiA of Salmonella enterica serovar Typhi is involved in virulence.

Salmonella enterica serovar Typhi causes a human-restricted systemic infection called typhoid fever. We have identified a Typhi genomic region encoding two ORFs, STY1498 and STY1499, that are expressed during infection of human macrophages and organized in an operon. STY1498 corresponds to clyA, which encodes a pore-forming cytolysin, and STY1499 encodes a 27 kDa protein, without any attributed function, which we have named TaiA (Typhi-associated invasin A). In order to evaluate the roles of these genes in Typhi pathogenesis, isogenic Typhi strains harbouring a non-polar mutation of either cly

Tumor cell AMPK activation enhances NK cell anti-tumor immunity and synergizes with PD-L1 blockade therapy.

Immune checkpoint blockade targeting the programmed cell death protein 1 (PD-1) or programmed death ligand 1 (PD-L1) pathway has shown great … l or genetic activation of AMPK in cancer cells sensitized them to NK cell-mediated killing through perforin and synergized with PD-L1 blockade therapy to suppress tumor growth in mice in an NK cell-dependent manner. Transcriptomic analyses revealed that AMPK activation in tumor cells triggered the expression of pattern recognition receptor genes and a che …

HVEM-LIGHT signaling promotes antibody-dependent neutrophil FcγR-mediated trogocytosis against herpes simplex virus infection.

Studies with a candidate vaccine deleted in glycoprotein D (ΔgD-2) for herpes simplex virus (HSV) prevention uncovered a role for herpes vir … uires their expression of HVEM and its ligand, LIGHT. Cytolysis is not associated with granzyme and perforin production but occurs by a trogocytosis-like pathway. Pharmacological inhibition of myosin light-chain kinase (MLCK), which mediates trogocytosis, inhibits cytolysis. Similar results were obtained when human neutrophils were cocultured with HSV-infe …

Lactate Enhances CD8+ T Cell Cytotoxicity Through H3K9la Upregulation to Drive Vitiligo Pathogenesis.

Vitiligo is characterized by epidermal melanocyte destruction, with autoreactive CD8+ T cells playing a central pathogenic role, yet the mec … in lesional skin. In vitro, lactate enhanced CD8+ T cell effector molecule expression (granzyme B, perforin, IFN-γ, CD107a) and cytotoxic function. Mechanistically, lactate increased global protein lactylation in CD8+ T cells, with marked enrichment at histone H3 lysine 9 (H3K9). H3K9 lactylation (H3K9la) was associated with enhanced chromatin accessibili …

Latent cytomegalovirus disrupts innate NK cell responses to P. falciparum and impairs parasite control in first infection in adults.

NK cells are innate and adaptive responders to malaria, with functional responses underpinned by NK cell heterogeneity. One driver of NK cel … es, was lower in CMV infected individuals. Linking NK cell activation to clinical outcomes, NK cell perforin expression was associated with parasite control in CMV seronegative individuals during first malaria infection. Data highlight the interplay between pathogens and the host-immune response that influence clinical outcomes.

Toxoplasma gondii infection reduces CD59 expression through downregulation of JAK2/STAT3 signaling axis to enhance decidual NK cell cytotoxicity via the RAS/MAPK pathway.

OBJECTIVE AND DESIGN: Toxoplasma gondii (T. gondii) infection disrupts pregnancy by modulating decidual natural killer (dNK) cells function. … ter. CD59 downregulation subsequently activated the Ras/MAPK pathway, leading to elevated IFN-γ and perforin production and enhanced cytotoxicity. Lack of cd59a exacerbated adverse pregnancy outcomes caused by T. gondii infection. CONCLUSIONS: T. gondii suppresses CD59 in dNK cells via JAK2/STAT3 inhibition, which enhances dNK cell cytotoxicity through Ra …

The Responsiveness of Breast Cancer Cells to Varied Levels of Vitamin B12, Cisplatin, and G-CSF.

Supportive agents, such as vitamin B12 (cobalamin, B12) and granulocyte colony-stimulating factor (G-CSF), are widely used during chemothera … cytotoxicity, suppressed caspase-3/-8/-9 activation, preserved mitochondrial integrity, and reduced perforin/granzyme expression, exhibiting stronger effects in MCF-7 cells. G-CSF markedly increased proliferation (>130% at 50 ng/mL), while B12 modestly enhanced viability and mitigated cisplatin-induced damage, particularly in triple-negative cells. These f …

Adoptive transfer of NK cells engineered with a CD5-based chimeric antigen receptor (SRCD5CAR) to treat invasive fungal infections.

The treatment of invasive fungal infections (IFIs) poses a major health challenge due to their severity, the scarcity and toxicity of curren … (i.e., CD69 expression and cytokine/chemokine production) and killing (i.e., CD107a expression and perforin/granzyme production) against different pathogenic fungal species (i.e., Candida albicans, Cryptococcus neoformans, Aspergillus fumigatus, and Fusarium solani). Further in vivo infusion of SRCD5CAR-NK cells into fungal-infected NSG mice increased sur …

CliCAR: A non-genetic CAR engineering strategy to empower NK cells for targeted cancer immunotherapy.

Conventional CAR-based immunotherapy has demonstrated promising efficacy in hematological malignancies. However, the inherently low transduc … nst HER2-positive cancer cells and enhanced immune activation, including increased levels of IFN-γ, perforin, and granzyme B. In vivo experiments, CliCAR-NK cells significantly suppressed HER2-positive tumor growth without observable toxicity in a xenograft model, supporting its therapeutic potential. Through this study, we introduce the CliCAR system as a …

Neuroimmune crosstalk in Parkinson's disease: the pivotal role of microglia and infiltrating T cells.

Parkinson’s disease (PD), the second most common neurodegenerative disorder, is characterized by progressive dopaminergic neuron loss in the substantia nigra and α-synuclein aggregation. Emerging evidence highlights the significant role of neuroimmune crosstalk in PD pathogenesis, particularly the interactions between microglia and infiltrating T cells. Disruption of the blood–brain barrier in PD facilitates infiltration of peripheral CD4 + and CD8 + T cells into the central nervous system. Activated CD8 + T cells exert direct neurotoxicity by releasing granzymes, perforin, and proinflammatory…

Boron Nitride Nanomaterials Trigger Immunomodulatory Effects in Human Broncho-Epithelial Cells by Modulating Eicosanoid Lipid Signaling.

For the successful commercial development of emerging 2D materials, it is crucial to understand their potential biological effects on health … cells reveals the activation of distinct lymphocyte populations expressing cytotoxic granzyme B and perforin mainly after exposure to conditioned medium from BNNT-exposed asthmatic HBE cultures. These findings unveil the sub-cytotoxic impact of BN nanomaterials on cellular lipid homeostasis and associated immunomodulation from repeated-dose exposures, whic …

The miR-451a facilitates natural killer cell-associated immune deficiency after ischemic stroke.

Ischemic stroke is a devastating neurological disease. Brain ischemia impairs systemic immune responses and heightens susceptibility to infe … a downregulation of activation marker CD69, and reduced production of effector molecules IFN-γ and perforin. Conversely, miR-451a inhibitor preserved NK cell activation and cytotoxicity, rescuing local inflammation, and reducing bacterial burden in the lung. Pharmacological inhibition of Akt-mTOR pathway with AZD8055 effectively blocked the impacts of miR …

CD20+ натуральные клетки убийц являются полифункциональными, похожими на память клетками, обогащенными воспаляющими расстройствами.

В то время как CD20 изначально был охарактеризован как маркер для клетки B, его выражение на клетках памяти T расширило наше понимание распределения и функции этой молекулы. Здесь мы идентифицируем ранее непризнанную популяцию клеток NK, выраженную CD20, и продемонстрируем ее функциональное значение. Клетки CD56+CD20+NK характеризуются признаками активации клеток, включая повышенную NKp46, CD69 и CD137 выражение, повышенную производительность и увеличение производства подстрекательских цитокинов (IFN-__, GM-CSF, TNF-α, IL-10). Функциональный анализ выявил повышенную цитотоксичность по отношени

Совпадение в аннотации оригинала
While CD20 was initially characterized as a B cell-specific marker, its expression on memory T cells has expanded our understanding of this … gets, correlating with increased expression of cytolytic mediators including granzymes A, B, and K, perforin, FASL, and TRAIL. Single-cell transcriptional profiling demonstrated that MS4A1-expressing NK cells possess a distinct molecular signature characterized by elevated granzyme K expression and memory-like features. These cells preferentially localize …

Цитотоксичные Т лимфоциты и их двойная роль в модуляции целостности мозгового барьера в неврологических патологиях с иммунной помощью.

Барьер крови и мозга (BBB) представляет собой динамический многоклеточный интерфейс, который сохраняет гомеостазиз центральной нервной системы (CNS) путем ограничения проникновения патогенов и циркуляционных клеток. Цитотоксичные лимфоциты (КТЛ), состоящие как из CD8+, так и CD4+, имеют ключевое значение для адаптивного иммунитета за счет целенаправленной ликвидации инфицированных или преобразованных клеток. Однако при иммунизированных неврологических расстройствах, включая вирусный энцефалит, множественный склероз, болезнь Паркинсона и глиома, функции эффекта CTL могут непреднамеренно подорва

Совпадение в аннотации оригинала
The blood-brain barrier (BBB) is a dynamic, multicellular interface that preserves central nervous system (CNS) homeostasis by restricting e … ineate three principal mechanisms by which CTLs modulate the BBB: (1) direct cytotoxicity, in which perforin/granzyme release and FasL-Fas interactions induce endothelial cell apoptosis; (2) proinflammatory cytokine signaling, notably IFN‑γ and TNF‑α activation of JAK/STAT and NF‑κB pathways in brain microvascular endothelial cells; and (3) chemokine‑drive …

PD-1+CD8+ T Cell-Mediated Hepatocyte Pyroptosis Promotes Progression of Murine Autoimmune Liver Disease.

The specific mechanisms underlying effector pathways in autoimmune liver disease remain enigmatic and therefore constructing appropriate mur … CD8+ T cells can induce the pyroptosis of hepatocytes through elevated production of granzyme B and perforin-1. These results provide a novel explanation for the cytotoxic activity of pathogenic liver PD-1+CD8+ T cells in autoimmune liver diseases and offer potential therapeutic targets.

Genetics of Macrophage Activation Syndrome in Systemic Juvenile Idiopathic Arthritis.

Macrophage activation syndrome (MAS) is a life-threatening episode of hyperinflammation driven by excessive activation and expansion of T cells (mainly CD8) and hemophagocytic macrophages producing proinflammatory cytokines. MAS has been reported in association with almost every rheumatic disease, but it is by far most common in systemic juvenile idiopathic arthritis (SJIA). Clinically, MAS is similar to familial or primary hemophagocytic lymphohistiocytosis (pHLH), a group of rare autosomal recessive disorders linked to various genetic defects all affecting the perforin-mediated cytolytic pat…

Pediatric CNS-isolated hemophagocytic lymphohistiocytosis with brain hemorrhages: a case report.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is an inherited syndrome characterized by immune dysregulation. Central nervous system … t per the HLH-1994 protocol and underwent stem cell transplantation. Two years post-transplant, his perforin expression is nearly normal and his neurologic deficits have significantly improved. CONCLUSIONS: This case illustrates the variability in presentation of isolated CNS-HLH. Although rare, it is important to include this diagnosis on the differentia …