Cell shape sensing licenses dendritic cells for homeostatic migration to lymph nodes

Nature Immunology, Год журнала: 2024, Номер 25(7), С. 1193 - 1206

Опубликована: Июнь 4, 2024

Immune cells experience large cell shape changes during environmental patrolling because of the physical constraints that they encounter while migrating through tissues. These can adapt to such deformation events using dedicated shape-sensing pathways. However, how sensing affects immune function is mostly unknown. Here, we identify a mechanism increases expression chemokine receptor CCR7 and guides dendritic migration from peripheral tissues lymph nodes at steady state. This relies on lipid metabolism enzyme cPLA

Язык: Английский

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Single-cell transcriptomics of bronchoalveolar lavage during PRRSV infection with different virulence

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 28, 2025

Porcine reproductive and respiratory syndrome virus (PRRSV) causes significant economic losses in the global swine industry due to its high genetic diversity different virulence levels, which complicate disease management vaccine development. This study evaluated longitudinal changes immune cell composition of bronchoalveolar lavage fluid clinical outcomes across PRRSV strains with varying virulence, using techniques including single-cell transcriptomics. In highly virulent infection, faster viral replication results an earlier peak lung-damage time point, marked by interstitial pneumonia, a decrease macrophages, influx lymphocytes. Viral tracking reveals less than 5% macrophages are directly infected, further analysis indicates bystander death, likely regulated exosomal microRNAs as factor. contrast, intermediate infection shows delayed point fewer population modifications. Furthermore, anti-inflammatory M2-like (SPP1-CXCL14high) identified their counts increase during contributing local defense lung recovery, is not observed infection. These findings provide comprehensive description cellular landscape differential mechanisms, will help build new hypotheses understand pathogenesis other infections. can have markedly pigs. Here, authors describe differences response suggest that may aid recovery health.

Язык: Английский

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Revolutionizing cancer treatment: The power of dendritic cell-based vaccines in immunotherapy

Biomedicine & Pharmacotherapy, Год журнала: 2025, Номер 184, С. 117858 - 117858

Опубликована: Фев. 16, 2025

Язык: Английский

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Single-cell profiling reveals pathogenic role and differentiation trajectory of granzyme K+CD8+ T cells in primary Sjögren’s syndrome

JCI Insight, Год журнала: 2023, Номер 8(8)

Опубликована: Март 7, 2023

Primary Sjogren's syndrome (pSS) is a systemic autoimmune inflammatory disease mainly defined by T cell–dominated destruction of exocrine glands. Currently, CD8+T cells were closely related to the pathogenesis pSS. However, single-cell immune profiling pSS and molecular signatures pathogenic have not been well elucidated. Our multiomics investigation identified that both cell B cell, especially cells, undergoing significant clonal expansion in patients. TCR clonality analysis revealed peripheral granzyme (GZM) K+CXCR6+CD8+T had higher proportion shared clones with CD69+CD103-CD8+ tissue resident memory (TRM) labial glands CD69+CD103-CD8+TRM featured high expression GZMK more active cytotoxic compared their CD103+ counterparts. Peripheral GZMK+CXCR6+CD8+T CD122 increased harbored gene signature similar TRM Consistently, IL-15 was significantly elevated plasma showed capacity promote differentiation into STAT5 dependent manner. Taken together, we depicted landscape further conducted comprehensive bioinformatics vitro experimental characterize role trajectory CD8+TRM

Язык: Английский

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New genetic and epigenetic insights into the chemokine system: the latest discoveries aiding progression toward precision medicine

Cellular and Molecular Immunology, Год журнала: 2023, Номер 20(7), С. 739 - 776

Опубликована: Май 17, 2023

Abstract Over the past thirty years, importance of chemokines and their seven-transmembrane G protein-coupled receptors (GPCRs) has been increasingly recognized. Chemokine interactions with trigger signaling pathway activity to form a network fundamental diverse immune processes, including host homeostasis responses disease. Genetic nongenetic regulation both expression structure conveys chemokine functional heterogeneity. Imbalances defects in system contribute pathogenesis variety diseases, cancer, inflammatory metabolic neurological disorders, which render focus studies aiming discover therapies important biomarkers. The integrated view biology underpinning divergence plasticity provided insights into dysfunction disease states, including, among others, coronavirus 2019 (COVID-19). In this review, by reporting latest advances results from analyses plethora sequencing-based datasets, we outline recent understanding genetic variations heterogeneity provide an updated contribution pathophysiological network, focusing on chemokine-mediated inflammation cancer. Clarification molecular basis dynamic chemokine-receptor will help advance achieve precision medicine application clinic.

Язык: Английский

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Immunotherapy response induces divergent tertiary lymphoid structure morphologies in hepatocellular carcinoma

Nature Immunology, Год журнала: 2024, Номер 25(11), С. 2110 - 2123

Опубликована: Окт. 25, 2024

Язык: Английский

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Cell Membrane‐Coated Nanoparticles: A New Frontier in Immunomodulation

Advanced NanoBiomed Research, Год журнала: 2024, Номер 4(8)

Опубликована: Май 31, 2024

Immune dysregulation is a pivotal factor in the onset and progression of various diseases. In cancer, immune system's inability to discern eliminate abnormal cells leads uncontrolled tumor growth. When faced with resilient pathogens or harmful toxins, system encounters challenges clearance neutralization. Achieving delicate balance pro‐inflammatory anti‐inflammatory signals essential managing range disorders Like other biomedical research domains, nanotechnology has provided innovative approaches for rebalancing host immunity. Among plethora nanotechnology‐based interventions, concept cell membrane‐coated nanoparticles holds significant potential immunomodulatory applications owing their biomimetic properties that allow precise interaction compromised system. This review thoroughly examines novel nanosystems modulation. The exploration covers crucial elements, including origins characteristics membranes, methods employed procurement coating, physicochemical/biological characterization techniques, enhancement therapeutic efficacy via functionalization. Subsequently, case studies‐based analysis utilizing these bioinspired tackling different conditions caused by disturbance been comprehensively discussed.

Язык: Английский

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Targeting lymph nodes for enhanced cancer vaccination: From nanotechnology to tissue engineering

Materials Today Bio, Год журнала: 2024, Номер 26, С. 101068 - 101068

Опубликована: Апрель 26, 2024

Lymph nodes (LNs) occupy a critical position in initiating and augmenting immune responses, both spatially functionally. In cancer immunotherapy, tumor-specific vaccines are blooming as powerful tool to suppress the growth of existing tumors, well provide preventative efficacy against tumorigenesis. Delivering these more efficiently LNs, where antigen-presenting cells (APCs) T abundantly reside, is under extensive exploration. Formulating into nanomedicines, optimizing their physiochemical properties, surface modification specifically bind molecules expressed on LNs or APCs, common routes have brought encouraging outcomes. Alternatively, porous scaffolds can be engineered attract APCs an environment for them mature, proliferate migrate LNs. A relatively new research direction inducing formation LN-like organoids, which shown positive relevance tumor prognosis. Cutting-edge advances directions discussions from future perspective given here, up-to-date pattern vaccination will drawn hopefully basic guidance studies.

Язык: Английский

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Defining the activity of pro-reparative extracellular vesicles in wound healing based on miRNA payloads and cell type-specific lineage mapping

Molecular Therapy, Год журнала: 2024, Номер 32(9), С. 3059 - 3079

Опубликована: Фев. 19, 2024

Small extracellular vesicles (EVs) are released by cells and deliver biologically active payloads to coordinate the response of multiple cell types in cutaneous wound healing. Here we used a injury model as donor pro-reparative EVs treat recipient diabetic obese mice, impaired We established functional screen for microRNAs (miRNAs) that increased activity identified down-regulation miR-425-5p vivo vitro associated with regulation adiponectin. tested type-specific reporter tetraspanin CD9 fusion GFP lineage map release from macrophages bed, based on expression macrophage-derived abundance EV sites. Analysis different promoters demonstrated under control macrophage-specific promoter was most abundant these were internalized dermal fibroblasts. These findings suggested miRNAs, such miR-425-5p, stimulate adiponectin has insulin-sensitizing properties. propose promote intercellular signaling between layers skin resolve inflammation, induce proliferation basal keratinocytes, accelerate closure.

Язык: Английский

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Initial IL-10 production dominates the therapy of mesenchymal stem cell scaffold in spinal cord injury

Theranostics, Год журнала: 2024, Номер 14(2), С. 879 - 891

Опубликована: Янв. 1, 2024

Spinal cord injury (SCI) is an acute damage to the central nervous system that results in severe morbidity and permanent disability. Locally implanted scaffold systems with immobilized mesenchymal stem cells (MSCs) have been widely proven promote locomotor function recovery SCI rats; however, underlying mechanism remains elusive.

Язык: Английский

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