A5032478236- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- IL-33, ST2, and ILC Pathways
- Epigenetics and DNA Methylation
- Neuroinflammation and Neurodegeneration Mechanisms
- Immune Response and Inflammation
- CAR-T cell therapy research
- Immune cells in cancer
- Cancer Immunotherapy and Biomarkers
- Viral Infections and Immunology Research
- Asthma and respiratory diseases
- Psoriasis: Treatment and Pathogenesis
- Eosinophilic Esophagitis
- Diabetes and associated disorders
- interferon and immune responses
- Cytomegalovirus and herpesvirus research
- Hepatitis C virus research
- HIV Research and Treatment
- Cancer, Hypoxia, and Metabolism
- Animal Virus Infections Studies
- Hematopoietic Stem Cell Transplantation
- Respiratory viral infections research
- Cancer Cells and Metastasis
- Atherosclerosis and Cardiovascular Diseases
Helmholtz Centre for Infection Research
2015-2024
RWTH Aachen University
2024
Luisenhospital Aachen
2024
Charité - Universitätsmedizin Berlin
2005-2012
German Rheumatism Research Centre
2005-2011
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....
Foxp3 activity is essential for the normal function of immune system. Two types regulatory T (T reg) cells express Foxp3, thymus-generated natural reg (nT cells, and peripherally generated adaptive (iT cells. These cell have complementary functions. Until now, it has not been possible to distinguish iT from nT in vivo based solely on surface markers. We report here that Neuropilin 1 (Nrp1) expressed at high levels by most cells; contrast, mucosa-generated other noninflammatory low Nrp1....
T cell activation requires that the meet increased energetic and biosynthetic demands. We showed exogenous nutrient availability regulated differentiation of naïve CD4(+) cells into distinct subsets. Activation under conditions glutamine deprivation resulted in their Foxp3(+) (forkhead box P3-positive) regulatory (Treg) cells, which had suppressor function vivo. Moreover, glutamine-deprived were activated presence cytokines normally induce generation helper 1 (TH1) instead differentiated...
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...
The forkhead-box protein P3 (Foxp3) is a key transcription factor for the development and suppressive activity of regulatory T cells (Tregs), cell subset critically involved in maintenance self-tolerance prevention over-shooting immune responses. However, transcriptional regulation Foxp3 expression remains incompletely understood. We have previously shown that epigenetic modifications CpG-rich Treg-specific demethylated region (TSDR) locus are associated with stable expression. now...
Compelling evidence suggests that Foxp3(+)CD25(+)CD4(+) Treg play a fundamental role in immunoregulation. We have previously demonstrated to enter peripheral tissues suppress ongoing inflammation. However, relatively little is known about how acquire the expression of homing receptors required for tissue- or inflammation-specific migration. Migratory properties conventional naïve T cells are shaped by tissue microenvironment and organ-specific dendritic during priming. Here, we show this...
It is emerging that CD4+Foxp3+ regulatory T (Treg) cells can produce the proinflammatory cytokine IFN-γ when stimulated in a Th1 environment. In this study, we report Foxp3+ Treg readily produced vivo highly inflammatory model of graft-versus-host disease (GVHD) and during Th1-dominated immune response to intracellular bacteria. Moreover, stimulation vitro via TCR presence IL-12 alone was sufficient induce production by dose-dependent manner. Transfer donor prevent lethal GVHD; therefore,...
Autoreactive Th1 and Th17 cells are believed to mediate the pathology of multiple sclerosis in central nervous system (CNS). Their interaction with microglia astrocytes CNS is crucial for regulation neuroinflammation. Previously, we have shown that only but not effectors activate microglia. However, it clear which targets CNS.To understand effects driven by CNS, induced experimental autoimmune encephalomyelitis wild-type mice CD4+ T cell-specific integrin α4-deficient where trafficking into...
Foxp3+ regulatory T (Treg) cells restrict immune pathology in inflamed tissues; however, an inflammatory environment presents a threat to Treg cell identity and function. Here, we establish transcriptional signature of central nervous system (CNS) that accumulate during experimental autoimmune encephalitis (EAE) identify pathway maintains function severe inflammation. This is dependent on the regulator Blimp1, which prevents downregulation Foxp3 expression "toxic" gain-of-function CNS....
"Suppressor T cells" were historically defined within the CD8(+) T-cell compartment and recent studies have highlighted several naturally occurring Foxp3(-) Treg populations. However, relevance of Foxp3(+) cells, which represent a minor population in both thymi secondary lymphoid organs nonmanipulated mice, remains unclear. We here demonstrate that de novo Foxp3 induction peripheral cells is counter-regulated by DC-mediated co-stimulation via CD80/CD86. fail to develop TCR-transgenic mice...
Gut-draining mesenteric lymph nodes (mLNs) are important for inducing peripheral tolerance towards food and commensal antigens by providing an optimal microenvironment de novo generation of Foxp3+ regulatory T cells (Tregs). We previously identified microbiota-imprinted mLN stromal as a critical component in induction. Here we show that this imprinting process already takes place the neonatal phase, renders cell compartment resistant to inflammatory perturbations later life. LN...
Th cells integrate signals from their microenvironment to acquire distinct specialization programs for efficient clearance of diverse pathogens or immunotolerance. Ionic have recently been demonstrated affect T cell polarization and function. Sodium chloride (NaCl) was proposed accumulate in peripheral tissues upon dietary intake promote autoimmunity via the Th17 axis. Here, we demonstrate that high-NaCl conditions induced a stable, pathogen-specific, antiinflammatory fate human vitro. The...
Basic processes of the fatty acid metabolism have an important impact on function intestinal epithelial cells (IEC). However, while role cellular oxidation is well appreciated, it not clear how de novo synthesis (FAS) influences biology IECs. We report here that interfering with FAS by deletion enzyme Acetyl-CoA-Carboxylase (ACC)1 in IECs results loss crypt structures and a specific decline Lgr5+ stem (ISC). Mechanistically, ACC1-mediated supports formation organoids differentiation complex...
We reported previously that a proportion of natural CD25(+) cells isolated from the PBMC HCV patients can further upregulate CD25 expression in response to peptide stimulation vitro, and proposed virus-specific regulatory T (Treg) were primed expanded during disease. Here we describe epigenetic analysis FOXP3 locus HCV-responsive show these are not activated conventional expressing FOXP3, but hard-wired Treg with stable phenotype function. Of approximately 46,000 genes analyzed genome wide...
Costimulatory signals by CD28 are critical for thymic regulatory T-cell (Treg) development. To determine the functional relevance of peripheral Treg post selection, we crossed widely used Forkhead box protein 3 (Foxp3)-CreYFP mice to bearing a conditional Cd28 allele. Treg-specific deficiency provoked severe autoimmune syndrome as result strong disadvantage in competitive fitness and proliferation CD28-deficient Tregs. By contrast, survival lineage integrity were not affected lack CD28. This...