Immunologic Research最新文献

Chimeric antigen receptor (CAR) therapies have expanded beyond T-cells with addition of natural killer (NK) cells. In ovarian cancer, long-term survival remains poor with the rising need for new therapies. Therefore, this meta-analysis evaluated the pre-clinical efficacy of emerging CAR-NK therapies in ovarian cancer models. Following PRISMA-guidelines and registered protocol (PROSPERO, CRD420251131530), literature from PubMed, Web of Science, and Scopus was retrieved till 30-06-2025 for pre-clinical in-vivo studies of CAR-NK therapy in ovarian cancer. Studies without in-vivo components or human CAR-NK were excluded. Primary outcomes were ratio of means (ROM) for tumor burden and median survival ratio (MSR). Data was analyzed in JASP™ and risk of bias (RoB) was determined using SYRCLE's RoB tool for animal studies. Fourteen experiments (21 CAR-NK groups) were included. CAR-NK significantly reduced tumor burden versus untreated controls (ROM 0.09 [0.03-0.32], p < 0.001) and unmodified/mock NK-cells (ROM 0.18 [0.08-0.42], p < 0.001). Survival was significantly prolonged (MSR 1.67 [1.31-2.14] vs. control; 1.40 [1.08-1.83] vs. unmodified/mock NK, both p < 0.05). Subgroup analyses revealed no significant modifiers, though trends favored mesothelin-targeted and NK-92-based CARs. Limited safety data indicated no cytokine release syndrome or graft-versus-host disease. Small sample size in subgroup analyses and unclear RoB in certain areas are some limitations of this study. However, the pooled estimates were robust to sensitivity analyses and relatively insignificant heterogeneity in survival outcomes could be important for poor long-term survival in ovarian cancers. CAR-NK demonstrates potential pre-clinical efficacy in ovarian cancer models, outperforming naive NK-cells with a consistent survival benefit.

Advanced glycation end products (AGEs), and particularly the unique AGE10 epitope, may be a potential biomarker of immunopathology in rheumatic diseases. They may be associated with inflammation, joint damage and ossification processes. AGE10 present in human and animal tissues could be detected with monoclonal antibody against melibiose-derived glycation product MAGE synthesized in anhydrous conditions. This MAGE product was different from the classic synthesis in water solution. The epitope was determined in serum with ELISA using these anti-MAGE monoclonal antibodies. This work aims to determine serum AGE10 levels in patients with reactive arthritis (ReA)-caused with Chlamydia trachomatis (group 2) and ReA with C. trachomatis during the reactivation of EBV infection (group 3). Additionally, ankylosing spondylitis (AS) patients (group 4) were involved in the study, due to the potential evolution of ReA toward AS. The control group maintained physiological AGE10 levels (316 µg/ml), while the combined infection group showed elevated AGE10 (850 µg/ml) compared to the chlamydial-only group (17 µg/ml). Fluorescent fAGE were at the highest level in AS patients. A striking finding was the complete absence of detectable AGE10 antigen in the AS group, coinciding with notably elevated immune complex AGE10-anti-AGE10 levels. A similar pattern was observed in patients with ReA caused by C. trachomatis alone (Group 2), albeit to a lesser extent. In contrast, both the control group and patients with ReA associated with EBV coinfection (group 3) displayed an inverse relationship, characterized by higher antigen levels and lower immune complex concentrations. Thus, diminished level of AGE10 could be caused, besides local accumulation, also by immune complexes formation, a pathogenic factor. Therefore, evaluating disease activity in ReA and AS is crucial to further our understanding of the pathophysiology of AGEs formation and predicting prognosis.

This study aims to investigate structural and expression-level alterations in the histone demethylase KDM4C gene in patients with rheumatoid arthritis (RA) and elucidate its role in the disease's epigenetic basis. KDM4C sequencing was performed in RA patients, and identified variants were mapped to functional domains, including the JmjN and PHD-type2 regions. KDM4C expression was assessed by quantitative PCR in RA and control groups. Molecular findings were analyzed alongside patients' clinical characteristics and treatment histories. A rare missense mutation (c.79 C > T, R27W) located in the JmjN domain was detected in a single patient with RA. In addition, a synonymous variant was identified in the PHD-type2 domain. The R27W variant is predicted by in silico analyses to impair protein homodimerization, while the synonymous change has been hypothesized to influence translational efficiency. Neither variant has previously been linked to RA. KDM4C mRNA expression was significantly reduced in patients with RA. This reduction was particularly evident in individuals with high CRP/ESR levels, positive RF and anti-CCP status, and treatment resistance. Taken together, the molecular and clinical findings suggest a potential functional alteration of KDM4C activity. Specifically, KDM4C may have a reduced capacity to remove repressive methylation marks on histone H3, particularly H3K9me3. These findings suggest that KDM4C dysregulation may promote a closed chromatin conformation in immune cells. This state may lead to silencing of genes involved in immune regulation and increased expression of inflammatory genes, thereby contributing to the pathogenesis of RA. KDM4C appears to be an important epigenetic regulator in RA pathogenesis. The coexistence of structural variants and decreased expression underscores its potential as a diagnostic biomarker and therapeutic target. To our knowledge, this is the first study providing integrated clinical and genetic evidence linking KDM4C dysregulation to RA.

The emerging role of Innate Lymphoid Cells (ILCs) in the pathogenesis and regulation of Multiple Sclerosis (MS), a complex neuroinflammatory autoimmune disease, has been increasingly recognized. Once identified only for activities conducted at barrier surfaces, ILCs are now understood to be important modulators of inflammation and tissue repair within the Central Nervous System (CNS). This review aims to elucidate the 'two sides of the coin' nature of ILCs in MS. ILCs are implicated in pathogenesis by driving neuroinflammation through pro-inflammatory cytokines, contributing to the formation of ectopic meningeal lymphoid follicles, and modulating meningeal immune system interactions. In contrast, certain ILC subsets confer protective effects by secreting anti-inflammatory cytokines and promoting tissue homeostasis. Recent experimental and clinical studies have demonstrated the complex balance and alteration of ILC responsiveness at various stages of MS. We focused on the importance of ILC subset determination, including their dependence on key cytokine signaling pathways and their critical role in the gut-CNS axis, a pivotal mediator of systemic immunity in MS. Moreover, the potential for ILC pathway targeting, either by modulating cytokine networks or modifying the microbiota, is discussed as a promising avenue for restoring immune balance, promoting neuroprotection and suppressing ILC-driven inflammation. Despite the challenges presented by ILC plasticity and diversity, elucidating ILC biology offers a clear path toward developing precise immunomodulatory strategies aimed at halting disease progression and promoting CNS repair in patients with MS.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease. Studies have reported that miR-452-5p is highly expressed in SLE, while RBL2 is downregulated. This study aims to investigate the diagnostic value of miR-452-5p in distinguishing healthy controls from SLE patients and its potential regulatory mechanisms in SLE. A total of 114 patients with SLE were included in this study. The expressions of miR-452-5p, RBL2, Foxp3, CD4, CD25, RORC and IL-17 A were detected by RT-qPCR. The diagnostic value of miR-452-5p was analyzed by ROC. Cell detection included proliferation and apoptosis experiments, which were determined by CCK-8 method and flow cytometry respectively. ELISA was used to determine the contents of IFN-γ, TNF-α, IL-6, TGF-β1 and IL-10 in the cell supernatant. DLR verified the binding relationship between miR-452-5p and RBL2. Compared with the healthy control group, the expression of miR-452-5p was upregulated. Its diagnostic value for SLE reaches 0.902. miR-452-5p targets and regulates RBL2. Excessive proliferation of PBMCs, reduced apoptosis and imbalance of Treg/Th17. After inhibiting miR-452-5p, the RBL2 level increased, the PBMC proliferation decreased, and apoptosis increased. The Treg marker genes Fxop3, CD4 and CD25 levels increased, while the Th17 marker genes RORC and IL-17 A levels decreased. Inhibiting RBL2 can reverse the above changes. miR-452-5p is expected to become a novel biomarker for SLE. miR-452-5p may affect the proliferation and apoptosis of PBMC and the balance of Treg/Th17 cells by targeting RBL2 mRNA, and participate in the immunopathological process of SLE.