Advanced immunophenotyping: A powerful tool for immune profiling, drug screening, and a personalized treatment approach

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Март 24, 2023

Various autoimmune diseases are characterized by distinct cell subset distributions and activation profiles of peripheral blood mononuclear cells (PBMCs). PBMCs can therefore serve as an ideal biomarker material, which is easily accessible allows for screening multiple types. A detailed understanding the immune landscape critical diagnosis patients with diseases, well a personalized treatment approach. In our study, we investigate potential multi-parameter spectral flow cytometry identification suffering from its power evaluation tool in vitro drug approaches (advanced immunophenotyping). We designed combination two 22-color immunophenotyping panels profiling distribution activation. Downstream bioinformatics analyses included percentages individual populations median fluorescent intensity defined markers were then visualized heatmaps dimensionality reduction approaches. testing epigenetic immunomodulatory drugs revealed altered status upon treatment, supports use high-throughput tool. Advanced might support exploration novel therapeutic contribute to future beyond.

Язык: Английский

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Pathogenesis and novel therapeutics of regulatory T cell subsets and interleukin-2 therapy in systemic lupus erythematosus

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Сен. 12, 2023

Systemic lupus erythematosus (SLE) is a heterogeneous multisystem inflammatory disease with wide variability in clinical manifestations. Natural arising CD4+ regulatory T cells (Tregs) play critical role maintaining peripheral tolerance by suppressing inflammation and preventing autoimmune responses SLE. Additionally, CD8+ cells, type 1 (Tr1), B also have less well-defined the pathogenesis of Elucidation roles various Treg subsets dedicated to immune homeostasis will provide novel therapeutic approach that governs for remission active lupus. Diminished interleukin (IL)-2 production associated depleted cell population, its reversibility IL-2 therapy provides important reasons treatment This review focuses on new therapeutics human low-dose benefits

Язык: Английский

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Interactions Between HDL and CD4+ T Cells: A Novel Understanding of HDL Anti-Inflammatory Properties

Arteriosclerosis Thrombosis and Vascular Biology, Год журнала: 2024, Номер 44(6), С. 1191 - 1201

Опубликована: Апрель 25, 2024

Several studies in animal models and human cohorts have recently suggested that HDLs (high-density lipoproteins) not only modulate innate immune responses but also adaptative responses, particularly CD4+ T cells. cells are central effectors regulators of the adaptive system, any alterations their homeostasis contribute to pathogenesis cardiovascular diseases, autoimmunity, inflammatory diseases. In this review, we focus on how components affect T-cell by modulating cholesterol efflux, synapsis, proliferation, differentiation, oxidative stress, apoptosis. While effects apoB-containing lipoproteins been relatively well established, review focuses specifically new connections between HDL We present a model where may through both direct indirect mechanisms.

Язык: Английский

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Immunomodulatory Role and Therapeutic Potential of HLA-DR ⁺ Regulatory T Cells in Systemic Lupus Erythematosus

Immunological Investigations, Год журнала: 2025, Номер unknown, С. 1 - 18

Опубликована: Март 11, 2025

Background Systemic lupus erythematosus (SLE) is a complex autoimmune disease that affects multiple organ systems. A key element in maintaining immune tolerance and preventing autoimmunity the role of regulatory T cells (Treg cells). Among these, HLA-DR+ Treg represent distinct subset, their altered expression functionality SLE are closely associated with progression disease. This review explores biological characteristics cells, mechanisms action SLE, as well potential challenges they pose therapeutic targets.

Язык: Английский

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The role of BATF in immune cell differentiation and autoimmune diseases

Biomarker Research, Год журнала: 2025, Номер 13(1)

Опубликована: Янв. 29, 2025

As a member of the Activator Protein-1 (AP-1) transcription factor family, Basic Leucine Zipper Transcription Factor (BATF) mediates multiple biological functions immune cells through its involvement in protein interactions and binding to DNA. Recent studies have demonstrated that BATF not only plays pivotal roles innate adaptive responses but also acts as crucial differentiation function various cells. Lines evidence indicate is associated with onset progression allergic diseases, graft-versus-host disease, tumors, autoimmune diseases. This review summarizes development cells, well immunoregulatory effects which may enhance current understanding pathogenesis diseases facilitate new therapeutic strategies.

Язык: Английский

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Unraveling the Microenvironment and the Pathogenic Axis of HIF‐1α–Visfatin–Fibrosis in Autoimmune Pancreatitis Using a Single‐Cell Atlas

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Янв. 31, 2025

Abstract Autoimmune pancreatitis (AIP) is identified as a severe chronic immune‐related disorder in pancreas, including two subtypes. In this study, pancreatic lesions patients diagnosed either type 1 AIP or 2 are examined, and these patients’ peripheral blood at single‐cell level. Furthermore, flow cytometry, immunofluorescence, functional assays performed to verify the cell AIP, there notable increase amount of B cells plasma cells, IgG4+ key pathogenic AIP. The differentiation path naïve‐stage into produced observed, an increased T helper follicular (Tfh) cells. This study also reveals that HIF‐1α, activated transcriptional factor, can directly bind promoter site NAMPT, promoting higher levels visfatin production HIF1A+ classical monocytes. Pancreatic stellate be by extracellular promote development fibrotic response across both current findings shed light on exploration dynamic alterations subgroups while elucidating subset potential fibrosis mechanism

Язык: Английский

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Human Umbilical Cord Mesenchymal Stem Cells for the Treatment of Systemic Lupus Erythematosus via Glucose Metabolism of CD4+T Cells

Stem Cell Reviews and Reports, Год журнала: 2025, Номер unknown

Опубликована: Фев. 20, 2025

T cells play a crucial role in the pathogenesis of systemic lupus erythematosus (SLE), with their functions regulated by various metabolic pathways. This study explores SLE and therapeutic effects human umbilical cord-derived mesenchymal stem (hUC-MSCs) via reprogramming. Clinical data peripheral blood samples were collected from 15 patients matched healthy controls. CD4+ isolated activated vitro anti-CD3/CD28. Following 72 h co-culture hUC-MSCs, cell viability was assessed using CCK-8 assay. The oxygen consumption rate (OCR) glycolytic proton efflux (glycoPER) measured Seahorse analyzer. Cytokine levels detected multiplex assay, transcriptome sequencing performed. Western blotting analyzed glucose metabolism-related enzymes signaling pathways model mice. Compared to controls, exhibited significantly increased OCR glycoPER (P < 0.05). OCR, glycoPER, viability, pro-inflammatory factors SLE-CD4+ decreased markedly 0.01). Upregulation 434 genes downregulation 172 observed, particularly JAK-STAT PI3K-Akt hUC-MSCs inhibited expression proliferation function aberrant modulating glycometabolism pathways, providing new insights into mechanisms MSCs based on

Язык: Английский

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Changes of Peripheral T Cells in Systemic Lupus Erythematosus Patients

Immunity Inflammation and Disease, Год журнала: 2025, Номер 13(2)

Опубликована: Фев. 1, 2025

ABSTRACT Background Efficient indicators for evaluating the imbalance of lymphocyte function were crucial to clinical therapy in systemic lupus erythematosus (SLE) patients. This study aimed find biomarkers assess lymphocyte‐mediated immune response SLE Methods A total 81 patients (non‐active: n = 35, active: 46) and 70 healthy donors recruited study. Peripheral blood was obtained, flow cytometry used detect circulating lymphocytes. Results Data showed that counts CD3 + T, CD4 CD8 NK cells decreased active compared with non‐active donors. The peripheral T increased responders but non‐responders among In addition, an increase B cell found those other two groups. Active higher percentages memory lower naive than controls. Activation molecules (CD38 HLA‐DR) inhibitory molecule PD‐1 expressions on significantly CD28 Conclusion indicated monitoring alterations surface may be helpful disease activity patients, even discriminate which beneficial choose best treatment option therapy.

Язык: Английский

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Integrative miRNA-mRNA profiling uncovers mechanisms of belimumab action in systemic lupus erythematosus

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Март 14, 2025

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder driven by autoreactive B cells and characterized the production of pathogenic autoantibodies. Belimumab, an anti-BAFF monoclonal antibody, has demonstrated efficacy in reducing disease activity corticosteroid use SLE patients, although responses remain variable. B-cell activating factor (BAFF) essential for cell survival autoantibody production, positioning it as key target pathogenesis. MicroRNAs (miRNAs), critical regulators gene expression immune homeostasis, have emerging role pathophysiology. However, their regulation response to therapies, such belimumab, remains unexplored. This study investigates miRNA-mRNA interactions T cells, myeloid from patients before after belimumab treatment. A total 79 miRNAs associated with treatment 525 miRNA-gene were identified. Validation 18 responders revealed significant changes miRNA but not cells. Belimumab was found modulate development regulating genes BLNK, BANK1, MEF2C, well CD40/CD40L axis. In influenced interferon signaling inflammatory cytokines via NF-κB activation. Changes downregulation KLF13, CCL5, IL4, appear be secondary modulation. These findings provide novel insights into miRNA-mediated regulatory networks underlying belimumab's immunomodulatory effects SLE. Further research required validate these through vitro experiments better understand guiding responses.

Язык: Английский

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Dysregulation of T Follicular Helper and Regulatory Cells in IRF5-SLE Homozygous Risk Carriers and Systemic Lupus Erythematosus Patients

Cells, Год журнала: 2025, Номер 14(6), С. 454 - 454

Опубликована: Март 19, 2025

T follicular helper (Tfh) and regulatory cells (Tfr) are required for antibody production dysregulated in SLE. Genetic variants within or near interferon factor 5 (IRF5) associated with SLE risk. We previously reported higher plasma autoantibodies healthy IRF5-SLE homozygous risk carriers. Here, we report the dysregulation of circulating Tfh Tfr both patients presymptomatic

Язык: Английский

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