A5010579045- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Epigenetics and DNA Methylation
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Diabetes and associated disorders
- CAR-T cell therapy research
- Cytomegalovirus and herpesvirus research
- Immune cells in cancer
- IL-33, ST2, and ILC Pathways
- Ovarian cancer diagnosis and treatment
- Renal Transplantation Outcomes and Treatments
- Single-cell and spatial transcriptomics
- Immunodeficiency and Autoimmune Disorders
- Immune responses and vaccinations
- Asthma and respiratory diseases
- Hematopoietic Stem Cell Transplantation
- BRCA gene mutations in cancer
- Atherosclerosis and Cardiovascular Diseases
- Dermatology and Skin Diseases
- Liver Diseases and Immunity
- Cancer Genomics and Diagnostics
- Reproductive System and Pregnancy
- Cancer-related molecular mechanisms research
- Lymphoma Diagnosis and Treatment
Precision for Medicine (United States)
2020-2024
University of South Florida
2022
Flinders Medical Centre
2022
Flinders University
2022
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
2022
University of Brescia
2022
NIHR Leeds Musculoskeletal Biomedical Research Unit
2019
University of Leeds
2019
Leeds Teaching Hospitals NHS Trust
2019
Heidelberg University
1997-2015
Compelling evidence suggests that the transcription factor Foxp3 acts as a master switch governing development and function of CD4+ regulatory T cells (Tregs). However, whether transcriptional control expression itself contributes to stable Treg lineage has thus far not been investigated. We here identified an evolutionarily conserved region within foxp3 locus upstream exon-1 possessing activity. Bisulphite sequencing chromatin immunoprecipitation revealed complete demethylation CpG motifs...
Abstract Compelling evidence suggests that Foxp3‐expressing CD25 + CD4 regulatory T cells (Treg) are generated within the thymus as a separate lineage. However, Foxp3 Treg can also be de novo in TGF‐β‐dependent process from naive by TCR triggering. Recently, we have shown naturally occurring, but not vitro TGF‐β‐induced display stable expression was associated with selective demethylation of an evolutionarily conserved element locus named TSDR (Treg‐specific demethylated region). Here,...
Abstract The transcription factor FOXP3 is critical for development and function of regulatory T cells (Treg). Their number functioning appears to be crucial in the prevention autoimmunity allergy, but also a negative prognostic marker various solid tumors. Although expression currently constitutes best‐known Treg, humans, transient observed activated non‐Treg. Extending our recent findings murine foxp3 locus, we epigenetic modification several regions human locus exclusively occurring Treg....
Abstract Regulatory T cells (Tregs) constitute an attractive therapeutic target given their essential role in controlling autoimmunity. However, recent animal studies provide evidence for functional heterogeneity and lineage plasticity within the Treg compartment. To understand better of human Tregs context type 1 diabetes, we characterized IFN-γ–competent subset CD4+CD127lo/−CD25+ Tregs. We measured frequency peripheral blood patients with diabetes by epigenetic analysis Treg-specific...
Abstract The adoptive transfer of CD4 + CD25 natural regulatory T cells (Treg) is a promising strategy for the treatment autoimmune diseases and prevention alloresponses after transplantation. Clinical trials exploring this require efficient in vitro expansion rare cell population. Protocols developed thus far rely on high‐grade purification Treg prior to culture initiation, process still hampered by lack cell‐specific surface markers. Depletion CD127 was shown separate activated...
Abstract Regulatory T-cells (Treg) have been the focus of immunologic research due to their role in establishing tolerance for harmless antigens versus allowing immune responses against foes. Increased Treg frequencies measured by mRNA expression or protein synthesis marker FOXP3 were found various cancers, indicating that dysregulation levels contributes tumor establishment. Furthermore, they constitute a key target immunomodulatory therapies cancer as well transplantation settings. One...
Abstract Stable expression of Foxp3 in regulatory T cells (Tregs) depends on DNA demethylation at the Treg-specific demethylated region (TSDR), a conserved, CpG-rich within locus. The TSDR is selectively ex vivo Tregs purified from secondary lymphoid organs, but it unclear which stage Treg development takes place. In this study, we show that commitment to stable lineage occurred during early stages murine thymic by engraving lineage-specific epigenetic marks parallel with establishment gene...
OBJECTIVE Autoimmune diseases, including type 1 diabetes, are thought to have a Th17-cell bias and/or T-regulatory cell (Treg) defect. Understanding whether this is hallmark of patients with diabetes crucial question that still unsolved, largely due the difficulties accessing tissues targeted by disease. RESEARCH DESIGN AND METHODS We phenotypically and functionally characterized Th17 cells Tregs residing in pancreatic-draining lymph nodes (PLNs) 19 63 nondiabetic donors those circulating...
Cell-surface CD25 expression is critical for maintaining immune function and homeostasis. As in few reported cases, deficiency manifests with severe autoimmune enteritis viral infections. To dissect the underlying immunological mechanisms driving these symptoms, we analyzed regulatory effector T cell functions a deficient patient harboring novel IL2RA mutation. Pronounced lymphoproliferation, mainly of CD8+ cells, was detected together an increase activation markers elevated serum cytokines....
Abstract Background Vitamin D levels are known to be associated with atopic disease development; however, existing data controversial. The aim of this study was investigate whether corresponding maternal and cord blood vitamin outcomes in early infancy. Methods Within the LINA cohort (Lifestyle environmental factors their Influence on Newborns Allergy risk), 25( OH ) measured samples 378 mother–child pairs during pregnancy at birth. Information about children's manifestations first 2 years...
Abstract Background: Regulatory T cells ( regs) with stable FOXP3 expression are characterized by a specific demethylated region in the gene reg‐specific region, TSDR ). The aim of this study was to analyse influence prenatal factors on cord blood reg numbers, as detected changes demethylation, and subsequent risk for allergic diseases. Methods: Analyses were performed within LINA samples from pregnant women (34th gestational week) n = 346 mother–child pairs). numbers via DNA demethylation ....
Abstract Objective Human articular chondrocytes do not express COL10A1 and undergo hypertrophy except in close vicinity to subchondral bone. In contrast, produced vitro from mesenchymal stem cells (MSCs) show premature expression cannot form stable ectopic cartilage transplants, which indicates that they may be phenotypically unstable suitable for treatment of lesions. CpG methylation established during natural development play a role suppression human chondrocytes. This study was undertaken...
The immune system plays a pivotal role in tumor establishment. However, the of T-lymphocytes within microenvironment as major cellular component adaptive effector response and their counterpart, regulatory T-cells (Treg), responsible for suppressive modulation, is not completely understood. This partly due to lack reliable technical solutions specific cell quantification solid tissues. Previous reports indicated that epigenetic marks cells, such Treg specifically demethylated region (TSDR)...
Immune cell profiles provide valuable diagnostic information for hematologic and immunologic diseases. Although it is the most widely applied analytical approach, flow cytometry limited to liquid blood. Moreover, either analysis must be performed with fresh samples or integrity needs guaranteed during storage transport. We developed epigenetic real-time quantitative polymerase chain reaction (qPCR) assays of human leukocyte subpopulations. After method establishment, whole blood from 25...
Presence of subclinical rejection (SCR) with IF/TA in protocol biopsies renal allografts has been shown to be an independent predictor factor graft loss. Also, intragraft Foxp3+ Treg cells patients SCR suggested differentiate harmful from potentially protective infiltrates. Nonetheless, whether presence Foxp3 and may protect a deleterious outcome not yet evaluated. This is case-control study which 37 the diagnosis 68 control no cellular infiltrates at 6-month matched for age time...
To understand the epigenetic alterations associated with assisted reproduction technology (ART) and reprogramming of gene expression that follows somatic cell nuclear transfer (SCNT), we screened a panel 41 amplicons representing 25 developmentally important genes on 15 different chromosomes (a total 1079 CpG sites). Methylation analysis was performed DNA from pools 80 blastocysts three classes embryos. This revealed subset distinguish between embryos developing in vivo, produced vitro, or...