Objective: Chronic HBV infection (CHB) exhausts HBV-specific T cells, develops epigenetic imprints that impair immune responses, and limits the effectiveness of immune checkpoint inhibitor (ICI) monotherapy, such as αPD-L1. This study aimed to determine whether the DNA methyltransferase inhibitor decitabine (DAC) could reverse these epigenetic imprints and enhance ICI efficacy in restoring HBV-specific T cell responses.
Methods: We investigated HBV-specific T cell responses by 10-day in vitro stimulation of peripheral blood mononuclear cells (PBMCs) from patients with CHB.
Background And Aims: Systemic Inflammation (SI) is considered a key mechanism in disease progression and development of complications in decompensated liver cirrhosis. SI is mainly driven by portal hypertension and bacterial translocation. Transjugular intrahepatic portosystemic shunt (TIPS)-insertion represents an effective treatment for portal hypertension.
View Article and Find Full Text PDFVaccination-induced protection against influenza is greatly diminished and increasingly heterogeneous with age. We investigated longitudinally (up to five time points) a cohort of 234 vaccinated >65-year-old vaccinees with adjuvanted vaccine FluAd across two independent seasons. System-level analyses of multiomics datasets measuring six modalities and serological data revealed that poor responders lacked time-dependent changes in response to vaccination as observed in responders, suggestive of systemic dysregulation in poor responders.
View Article and Find Full Text PDFBackground And Aims: Non-selective beta-blockers (NSBB) are a well-established treatment in patients with clinically significant portal hypertension. However, their potential role after insertion of a transjugular intrahepatic portosystemic shunt (TIPS) still needs to be determined. Of note, recent studies suggested that favourable anti-inflammatory effects of NSBB might be independent from pressure reduction.
View Article and Find Full Text PDFBackground: Urate concentration and the physiological regulation of urate homeostasis exhibit clear sex differences. DNA methylation has been shown to explain a substantial proportion of serum urate variance, mediate the genetic effect on urate concentration, and co-regulate with cardiometabolic traits. However, whether urate concentration is associated with DNA methylation in a sex-dependent manner is unknown.
View Article and Find Full Text PDFObjective: Hyperuricaemia is necessary for gout. High urate concentrations have been linked to inflammation in mononuclear cells. Here, we explore the role of the suppressor of cytokine signaling 3 (SOCS3) in urate-induced inflammation.
View Article and Find Full Text PDFImmune responses are tightly regulated yet highly variable between individuals. To investigate human population variation of trained immunity, we immunized healthy individuals with Bacillus Calmette-Guérin (BCG). This live-attenuated vaccine induces not only an adaptive immune response against tuberculosis but also triggers innate immune activation and memory that are indicative of trained immunity.
View Article and Find Full Text PDFBackground: Endogenous steroid hormones have significant effects on inflammatory and immune processes, but the immunological activities of steroidogenesis precursors remain largely unexplored.
Methods: We conducted a systematic approach to examine the association between steroid hormones profile and immune traits in a cohort of 534 healthy volunteers. Serum concentrations of steroid hormones and their precursors (cortisol, progesterone, testosterone, androstenedione, 11-deoxycortisol and 17-OH progesterone) were determined by liquid chromatography-tandem mass spectrometry.
Atopic dermatitis (AD) is a common inflammatory skin condition and prior genome-wide association studies (GWAS) have identified 71 associated loci. In the current study we conducted the largest AD GWAS to date (discovery N = 1,086,394, replication N = 3,604,027), combining previously reported cohorts with additional available data. We identified 81 loci (29 novel) in the European-only analysis (which all replicated in a separate European analysis) and 10 additional loci in the multi-ancestry analysis (3 novel).
View Article and Find Full Text PDFBacillus Calmette-Guérin vaccine is well known for inducing trained immunity in myeloid and natural killer cells, which can explain its cross-protective effect against heterologous infections. Although displaying functional characteristics of both adaptive and innate immunity, γδ T-cell memory has been only addressed in a pathogen-specific context. In this study, we aimed to determine whether human γδ T cells can mount trained immunity and therefore contribute to the cross-protective effect of the Bacillus Calmette-Guérin vaccine.
View Article and Find Full Text PDFEpigenetics functions as a bridge between host genetic & environmental factors, aiding in human health and diseases. Many immune-related diseases, including infectious and allergic diseases, have been linked to epigenetic mechanisms, particularly DNA methylation. In this review, we summarized an updated overview of DNA methylation and its importance in personalized medicine, and demonstrated that DNA methylation has excellent potential for disease prevention, diagnosis, and treatment in a personalized manner.
View Article and Find Full Text PDFBacillus Calmette-Guérin (BCG) vaccination is a prototype model for the study of trained immunity (TI) in humans, and results in a more effective response of innate immune cells upon stimulation with heterologous stimuli. Here, we investigate the heterogeneity of TI induction by single-cell RNA sequencing of immune cells collected from 156 samples. We observe that both monocytes and CD8 T cells show heterologous transcriptional responses to lipopolysaccharide, with an active crosstalk between these two cell types.
View Article and Find Full Text PDFMetabolic processes play a critical role in immune regulation. Metabolomics is the systematic analysis of small molecules (metabolites) in organisms or biological samples, providing an opportunity to comprehensively study interactions between metabolism and immunity in physiology and disease. Integrating metabolomics into systems immunology allows the exploration of the interactions of multilayered features in the biological system and the molecular regulatory mechanism of these features.
View Article and Find Full Text PDFSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes severe COVID-19 in some patients and mild COVID-19 in others. Dysfunctional innate immune responses have been identified to contribute to COVID-19 severity, but the key regulators are still unknown. Here, we present an integrative single-cell multi-omics analysis of peripheral blood mononuclear cells from hospitalized and convalescent COVID-19 patients.
View Article and Find Full Text PDFChildhood allergic diseases, including asthma, rhinitis and eczema, are prevalent conditions that share strong genetic and environmental components. Diagnosis relies on clinical history and measurements of allergen-specific IgE. We hypothesize that a multi-omics model could accurately diagnose childhood allergic disease.
View Article and Find Full Text PDFThe ongoing Coronavirus Disease 2019 (COVID-19) pandemic is caused by the highly infectious Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). There is an urgent need for biomarkers that will help in better stratification of patients and contribute to personalized treatments. We performed targeted proteomics using the Olink platform and systematically investigated protein concentrations in 350 hospitalized COVID-19 patients, 186 post-COVID-19 individuals, and 61 healthy individuals from 3 independent cohorts.
View Article and Find Full Text PDFMyeloid cells, crucial players in antitumoral defense, are affected by tumor-derived factors and treatment. The role of myeloid cells and their progenitors prior to tumor infiltration is poorly understood. Here we show single-cell transcriptomics and functional analyses of the myeloid cell lineage in patients with non-medullary thyroid carcinoma (TC) and multinodular goiter, before and after treatment with radioactive iodine compared to healthy controls.
View Article and Find Full Text PDFBackground & Aims: Chronic hepatitis C virus (HCV) infection can be cured with direct-acting antivirals (DAAs). However, not all sequelae of chronic hepatitis C appear to be completely reversible after sustained virologic response (SVR). Recently, chronic viral infections have been shown to be associated with biological age acceleration defined by the epigenetic clock.
View Article and Find Full Text PDFPolymers (Basel)
August 2022
Two polysaccharides from L. (CTLP-1 and CTLP-2) were purified, and their structures were analyzed by physical and chemical testing. CTLP-1 had a mass of 5900 Da that was composed of arabinose, glucose, and galactose with a mass molar ratio of 6.
View Article and Find Full Text PDF