BAMBI: A novel regulator of intestinal epithelial integrity in the control of colitis and colon cancer progression.

Genome-wide transcriptome profiling in crossbred pigs after challenge with Classical Swine Fever Virus.

Elevated CD3+ T-cell proportions and a dysregulated cytokine network characterize the Serofast state in treated primary syphilis: A cross-sectional study of 60 participants.

Ebola virus (EBOV) causes a severe, potentially fatal, disease, with outcome likely related to both viral and host factors. There is a clear correlation between viral load and outcome (survival/death) and inflammatory as well as other cellular pathways are differentially activated in the acute stage between patients who go on to survive versus those who go on to die. Age and sex may influence the course of Ebola virus disease (EVD) with potential differences at the molecular level. To investigate whether there were age and/or sex-specific differences in patients with EVD, previously published data from an RNAseq analysis of the blood transcriptome in patients from the 2013-2016 West African outbreak was stratified according to age/sex of the individual. This was correlated with the outcome of infection. Similar to the previously published data, immune responses were downregulated during the acute phase in hospitalised survivors compared to hospitalized fatal cases, regardless of the sex of the patient. However, aspects of the blood transcriptome/host response differed between females and males and certain age groups at the transcriptomic level. Genes associated with the lymphocyte differentiation pathway decreased in expression level with age in hospitalised fatal cases. However, this was the opposite in hospitalised survivors. From a medical countermeasure perspective, the work indicated that selection of animal models should consider age and sex, depending on the research question, and cellular pathways were identified that could be chemotherapeutically enhanced to promote survival.

CARD11 is a scaffold protein expressed primarily in hematopoietic tissues, shaping key processes in B and T cells via regulation of Ag-linked signaling pathways, including NF-κB, mTOR, JNK, and AKT. Heterozygous, gain-of-function (GOF) variants in its encoding gene, CARD11, are implicated in a human disorder characterized by frequent upper respiratory infections, poor responses to polysaccharide vaccines, vulnerability to certain opportunistic viruses, and polyclonal B-cell expansion, likely predisposing these patients to lymphoma. Over the past decade, several studies have elucidated some of the B-cell functional defects that likely underlie the patients’ infectious phenotype. However, the potential contributions of CARD11 GOF variants to subpopulations of T cells have not been explored in detail. Therefore, our study sought to investigate the effect of increased CARD11 activity on the development, maturation, activation, differentiation, and effector function of adaptive lymphocytes from a cohort of five individuals harboring monoallelic CARD11 GOF variants through detailed ex vivo immunophenotyping and in vitro analyses. Our findings revealed intrinsic requirements for CARD11 in activation, differentiation, and effector function of human naïve B cells. Contrary to previous reports, intact CARD11 activity is also required for multiple aspects of CD4+ T-cell homeostasis alongside its notable role in the humoral immune response. Overall, these results shed light on mechanisms underlying disease pathogenesis due to not only CARD11 GOF variants but also LOF variants and reveal opportunities to consider targeted therapies in CARD11 GOF patients.

Acute rejection (AR) remains the most common complication after heart transplantation (HT). AR is an acute immune response mediated by lymphocytes, and very late antigen-4 (VLA-4) plays a vital role in lymphocyte differentiation and transport, making it an attractive target for developing molecular diagnostic agents. In this study, we proposed the construction of a radionuclide probe 68Ga-LLP2A and explored the role of the VLA-4 receptor distribution in AR. The in vitro and in vivo targeting efficiency and specificity of the tracer were validated by the cell uptake assay of monocyte cells and cardiomyocytes, PET/CT imaging, and biodistribution of VLA-4-positive B16F10 tumor-bearing mice models, respectively. 68Ga-LLP2A (5.5-7.4 MBq/rat) were injected into each group of rats 5 days after transplantation, including allograft (ALL), allograft treatment (ALL-T), allograft blocking (ALL-B), isograft (ISO), and normal Lewis (NOR) rats. PET/CT images, ex vivo autoradiography, and biodistribution were performed 1 h after injection. Expression levels of VLA-4 in the hearts of rats in each group were assessed by immunochemical staining. The tracer exhibited high accumulation with good contrast in the graft heart of ALL rats in static PET/CT images, autoradiography, and biodistribution studies and lower accumulation of radioactivity in the ALL-T and ALL-B groups, while no uptake was seen in the ISO and NOR groups. Histological analysis confirmed the abundant infiltration of VLA-4-positive cells in the graft heart of ALL rats. In conclusion, 68Ga-LLP2A exhibited high VLA-4 targeting efficacy in vivo and could accumulate specifically in the graft heart, rendering it a promising candidate for noninvasive imaging of acute cardiac rejection.

Peripheral immunosenescence has been increasingly implicated in dementia pathogenesis. However, the contributions of specific lymphocyte subsets to cognitive outcomes remain poorly defined, and evidence from large-scale longitudinal studies is scarce. We leveraged data from the US Health and Retirement Study (n = 7444; mean age: 67.7 ± 9.7 years). Our primary analysis calculated three ratio metrics to quantify T-cell immunosenescence: the CD4:CD8 ratio, CD4 + EMRA: Naïve and CD8 + EMRA: Naïve ratios. Their longitudinal associations with 6-year cognitive decline were evaluated by linear mixed model adjusted for multiple covariates. We found that a higher CD8 + EMRA: Naïve ratio was significantly associated with accelerated cognitive decline (-0.050 point/year per SD; 95% CI: -0.066 to -0.033, P < 0.001). A nonlinear association was observed for the CD4:CD8 ratio (P for nonlinearity = 0.033), with only an intermediate level (the third quartile) associated with a slower cognitive decline. No significant association was found for the CD4 + EMRA: Naïve ratio. This study reveals a compartmentalized pattern in the associations of immunosenescent metrics with cognitive aging. The findings indicate a specific detrimental pathway characterized by an elevated CD8 + EMRA:Naïve ratio, whereas balanced CD4:CD8 homeostasis may play a beneficial role.

Ningxue shengban decoction regulates T-cell immune balance in immune thrombocytopenia via the bone marrow hematopoietic microenvironment.

BackgroundCholangiocarcinoma (CCA) is a rare cancer, with limited understanding of genetic and prognostic determinants. We aimed to explore genetic risk factors, assess their prognostic implications and evaluate associated systemic and intratumoral features.MethodsWe screened the UK Biobank to identify single-nucleotide polymorphisms (SNPs) potentially associated with intrahepatic CCA (International Classification of Diseases, 10th Revision (ICD-10) code: C22.1). Candidate SNPs were genotyped in a real-life cohort of 221 patients undergoing liver resection for intrahepatic or perihilar CCA at Charité – Universitätsmedizin Berlin. Intratumoral gene expression and pathway co-expression were examined. Serum proteomic profiles were evaluated in patients with intrahepatic CCA and the overall population.ResultsIn exploratory analyses, the telomerase reverse transcriptase (TERT) rs10069690 T allele was associated with a reduced risk of intrahepatic CCA (T allele vs C/C homozygotes: adjusted OR 0.824 (95% CI 0.713 to 0.951), p=0.008). However, T allele carriers undergoing liver resection for CCA had independently shorter overall survival (OS) compared with C/C homozygotes (median OS 21 (17–25) months vs 31 (24–38) months, p=0.034, HR 1.427 (1.023–1.991)). In serum proteomic analyses of the general population, presence of the T allele was associated with differences in immune-related pathways, including signatures consistent with increased lymphocyte differentiation and reduced NK-cell-mediated cytotoxicity. In intrahepatic CCA tumours, higher TERT mRNA expression was positively correlated with gene expression patterns consistent with increased cell cycle activity and regulatory T cell signatures, and negatively associated with pathways of cell differentiation, adhesion and immune effector function.ConclusionsThese exploratory, hypothesis-generating findings suggest that the TERT rs10069690 variant may be associated with intrahepatic CCA risk and clinical outcomes, as well as with immune-related and proliferative pathways. The observed context-dependent associations warrant independent validation and further functional investigation.

Background:Liver and lymph node endothelial cell C-type lectin (LSECtin) loss in liver sinusoidal endothelial cells (LSECs) during cirrhosis favors hepatic pro-inflammatory T-cell infiltration. We characterize histone protein post-translational modifications and DNA methylation in LSECs that may control LSECtin expression and evaluate methyltransferase inhibitors' capacity to retrieve LSECtin.Methods:DNA-methylation levels and histone post-translational modifications were studied by methylation array and ChIP-Seq experiments carried out on LSECs isolated by FACS from control and cirrhotic mice. Immortalized LSECs were treated with epigenetic effector inhibitory drugs (OTS186935-Suv39h2i, UNC0642-G9a/Glpi, UNC1999-EZH2/1i, 5-Aza-2’-deoxycitidine-DNMTi), alone and with IL-4, an LSECtin expression inducer. Drugs with regulatory potential were tested in vivo. LSECtin gene and protein expression, lymphocyte differentiation, and Th17-subpopulation proliferation were studied.Results:H3K9me3 and H3K27Me3 were reduced in LSECs of cirrhotic versus control mice. Suv39h2 and Ezh2/1 methyltransferase inhibitors OTS186935 and UNC1999, respectively, reduced Clec4g/LSECtin expression in immortalized LSECs. Murine primary LSECs showed H3K27me3 and H3K9me3 significantly enriched (controls) and reduced (cirrhotics) regions located upstream of the Clec4g promoter. OTS186935 and UNC1999 treated immortalized LSECs reduced H3K9me3 and H3K27me3 enrichment in these regions. Clec4g/LSECtin expression was also controlled by DNA methylation, as confirmed by Clec4g/LSECtin induction after 5-Aza-2’-deoxycitidine-DNMTi treatment in vitro and in vivo. Epigenetic drugs induced LSECtin in LSECs, contracted the hepatic Th17 compartment, attenuated hepatic structural damage, and improved liver function in cirrhosis.Conclusion:H3K9me3 and H3K27me3, and DNA-methylation regulate Clec4g expression in LSECs during cirrhosis. Inhibitory epigenetic-enzyme drugs increase Clec4g/LSECtin expression and provide evidence on relevant genomic regions for Clec4g reprogramming. The LSECtin-modulated hepatic Th17 compartment is contracted in cirrhosis by targeting these modifications.

Integrated determinants of multiple sclerosis susceptibility: Genetics, environment, infection and the microbiota.

A novel self-amplified RNA vaccine co-expressing NA and HA1 delivered by Salmonella confers potent protection against H9N2 influenza in chickens.

Cesarean scar pregnancy (CSP), a condition characterised by inflammation, occurs in 0.2% of women with a history of cesarean section(s), and is clinically categorised by type 1 and type 2 according to the ultrasound findings. Recent studies reported that systemic inflammation indices derived from routine whole-blood tests may serve as additional clinical predictive markers for early CSP detection, with lymphocyte counts showing a reduction. However, the specific lymphocyte populations contributing to this reduction remain unclear. This study included 72 women diagnosed with CSP and 50 gestation-matched controls. The subsets of peripheral lymphocytes, including CD45 lymphocytes/monocytes, CD3 T cells, CD4 T helper cells, CD8 cytotoxic T cells, CD19 B cells, total NK cells and NKT-like cells, were measured. We found a significant reduction in peripheral total NK cells and CD8 cytotoxic T cells in CSP women compared to controls. However, there were no differences in peripheral immune cell profiles between type 1 and type 2 CSP. Using total NK cell counts with a cut-off value of 210/µl, the area under the curve (AUC) was 0.698, with a sensitivity of 64%. Our findings suggest that the reduction in peripheral total NK cells and CD8 T cytotoxic cells may play a role in the development of CSP. Additionally, peripheral total NK cell counts, derived from routine whole-blood tests, could serve as a predictive marker for early CSP diagnosis.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12865-026-00841-9.

Graphene quantum dots (GQDs) belong to the carbon quantum dot family, with low toxicity, high biocompatibility, and excellent colloidal stability. Mesoporous silica nanoparticles (MSNs) are recognized as effective drug delivery systems due to their high drug-loading capacity, while glucosamine sulfate (GS) exhibits immunemodulatory properties. In this study, to maximize the immune effect of GS, a graphene quantum dot-coated mesoporous silica loaded with glucosamine sulfate (MSN-G-Q) is synthesized, and its immunoactivation effects are evaluated in vitro and in vivo. In vitro, MSN-G-Q enhances macrophage uptake activity, stimulates nitric oxide (NO) production, and upregulates CD80+ and CD86+ expression. In vivo, MSN-G-Q/OVA increases immune organ index, facilitates dendritic cell (DC) maturation, promotes T lymphocyte proliferation and differentiation, elevates antigen-specific IgG antibodies and cytokines, including IFN-γ, IL-4, and IL-1β, and prolongs ovalbumin (OVA) residence in immune organs and lymph nodes. The results show that MSN-G-Q/OVA is a promising immunostimulatory antigen delivery system.

Cationic Chinese yam polysaccharides nanoparticles-based Pickering emulsion for delivery vaccine and adjuvant to enhance immune response.

TRIF signaling is essential for the activation of dendritic cells during porcine rotavirus infection.

Postoperative complications such as tumor recurrence, wound infections, and delayed tissue regeneration persist as critical challenges in melanoma management. In this study, we designed a temperature-tunable photothermal immunotherapy hydrogel dressing (Pd/JQ1@SerMA) to overcome these melanoma postoperative complications. Specifically, this immunomodulatory dressing is composed of methacrylic anhydride-modified sericin (SerMA), palladium nanosheets (Pd) with excellent photothermal performance, and the small-molecule BRD4 inhibitor JQ1. The Pd/JQ1@SerMA hydrogel induces immunogenic cell death (ICD) in tumor cells via high-temperature photothermal effects (> 48 °C), while the released JQ1 downregulates interferon-γ-induced programmed death ligand 1 (PD-L1) expression, thereby mitigating acquired immune resistance and enhancing antitumor immunity. The transcriptomic profiling revealed significant activation of tumor-specific immune pathways, including lymphocyte differentiation, T-cell activation, and systemic immune responses. In addition, the high-temperature photothermal effects (> 48 °C) eliminates over 95% of Staphylococcus aureus and Escherichia coli. Notably, the hydrogel adaptively fills irregular wound defects, and accelerates postoperative tissue regeneration under mild photothermal stimulation (~ 42 °C). In conclusion, this temperature-tunable photothermal immunotherapeutic hydrogel exhibits remarkable clinical potential for preventing tumor recurrence, combating infection, and promoting wound healing.Graphical Supplementary InformationThe online version contains supplementary material available at 10.1186/s12951-026-04292-7.

We investigated how selective inhibition of galectin-1 and galectin-3 expressed by COLO 201 colorectal adenocarcinoma cells modulates CD4+ T lymphocyte differentiation in vitro. The mRNA expression levels of the transcription factors T-bet (TBX21), RORC2, and Foxp3 were analyzed in peripheral blood mononuclear cells (PBMCs) from colorectal cancer patients and healthy donors following co-culture with COLO 201 cells in the presence of galectin-1 inhibitor OTX 008, galectin-3 inhibitor GB1107, or both. Inhibition of galectin-1 in co-cultures increased TBX21 and RORC2 mRNA expression while suppressing FOXP3 in PBMCs from both groups. In patient-derived PBMCs, galectin-3 inhibition produced a similar effect. Conversely, in healthy donor cells, galectin-3 blockade suppressed RORC2 and induced FOXP3 expression. Notably, the most pronounced downregulation of FOXP3 was achieved by simultaneously inhibiting both galectins.

Qigong is an ancient Chinese psychosomatic system with a fascinating holistic approach to health, which exerts remarkable physical and mental benefits. Nevertheless, this method has been scarcely investigated in fibromyalgia, and although a significant amount of research has focused on the immune effects of qigong, its action on immune parameters of individuals with fibromyalgia has never been studied to date. Thus, the aim of the present study was, therefore, to explore the effects of a qigong programme on white blood cells and other immune parameters in individuals with this syndrome. 39 individuals participated in the study, 16 in the experimental group and 23 in the control. Experimental individuals participated in a 4-week qigong programme. Blood samples for the quantification of immune parameters (leukocyte count, number and percentage of specific leukocyte and lymphocyte subsets, as well as concentrations of immunoglobulins and complement) were drawn from all participants before the experiment commenced and after it concluded. The experimental group displayed a significantly lower value in the number of specific lymphocytes subsets such as CD3, CD4, CD8, CD16, CD45, as well as in the percentage of total lymphocytes. In addition, the experimental group exhibited a greater percentage of CD19 and a higher concentration of C3. The practice of qigong for a short period of 1 month was associated with significant changes of diverse immunological biomarkers in individuals with fibromyalgia. These changes were characterized by a higher number of numerous lymphocyte subsets, while at the same time a lower concentration of C3 and of the percentage of some lymphocyte subtype in these individuals. While it is tempting to speculate the implications of the broad immunomodulation associated with qigong practice in fibromyalgia syndrome, further research into the immune effects of this Taoist mind-body practice is needed.

Introduction: Membranous nephropathy constitutes a significant proportion of cases leading to end-stage renal disease. In such instances, the accurate distinction between primary and secondary forms is crucial for proper treatment. Consequently, we systematically examined the link between genetically predicted membranous nephropathy and various diseases. Methods: The phenome-wide association approach assessed the links between genetically predicted membranous nephropathy and 2,408 diseases. Two-sample Mendelian randomization was then employed to explore causal relationships using methods like inverse variance weighting, MR-Egger, weighted median, and others. A replication analysis was conducted to confirm these associations. Gene enrichment analysis was conducted using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses to explore potential pathogenic mechanisms. Results: A statistically significant association was noted between genetically predicted Graves’ disease, thyrotoxicosis, and thyrotoxicosis with diffuse goiter and an elevated risk of membranous nephropathy. Subsequent replication analysis for Graves’ disease demonstrated consistent results. Functional analysis suggests that Graves’ disease may affect membranous nephropathy by influencing pathophysiological mechanisms and pathways related to the proliferation and differentiation of lymphocytes and leukocytes, adhesion between leukocytes and cells, differentiation of CD4+ αβ T cells, and differentiation of Th1 and Th2 cells. Conclusion: Our study indicates that genetically predicted thyrotoxicosis, thyrotoxicosis with diffuse goiter, and Graves’ disease are correlated with an increased likelihood of membranous nephropathy. Graves’ disease may affect membranous nephropathy development by influencing leukocyte proliferation and differentiation. Additional research is warranted to validate these findings and ascertain their relevance in clinical management.