A5059836273- Immune Cell Function and Interaction
- Diabetes and associated disorders
- Helicobacter pylori-related gastroenterology studies
- Macrophage Migration Inhibitory Factor
- T-cell and B-cell Immunology
- Pancreatic function and diabetes
- Diabetes Management and Research
- Signaling Pathways in Disease
- IL-33, ST2, and ILC Pathways
- Vitamin D Research Studies
- NF-κB Signaling Pathways
- Adipokines, Inflammation, and Metabolic Diseases
- Regulation of Appetite and Obesity
- Galectins and Cancer Biology
- Immunodeficiency and Autoimmune Disorders
- Immunotherapy and Immune Responses
- RNA modifications and cancer
- Atherosclerosis and Cardiovascular Diseases
- Adipose Tissue and Metabolism
- Inflammatory Bowel Disease
- Circular RNAs in diseases
- Biochemical Analysis and Sensing Techniques
- CRISPR and Genetic Engineering
- Dietary Effects on Health
- Sphingolipid Metabolism and Signaling
Ludwig-Maximilians-Universität München
2019-2025
German Center for Diabetes Research
2016-2024
Heinrich Heine University Düsseldorf
2017-2024
Deutsches Diabetes-Zentrum e.V.
2017-2024
Helmholtz Zentrum München
2014-2024
Institute of Diabetes Research
2014-2022
Center for Environmental Health
2013
University of Lausanne
2012
Friedrich-Alexander-Universität Erlangen-Nürnberg
2012
Johannes Gutenberg University Mainz
2012
A number of recent studies testify that calcitriol alone or in combination with corticosteroids exerts strong immune modulatory activity. As a new approach, we evaluated the protolerogenic potential and dexamethasone acute T helper (Th)1-mediated colitis mice. rectal enema trinitrobenzene sulfonic acid (TNBS) (100 mg/kg) was applied to BALB/c Calcitriol and/or were administered i.p. from days 0 3 5 following instillation haptenating agent. Assessment severity performed daily. Colon tissue...
Cell-cell interactions in the central nervous system play important roles neurologic diseases. However, little is known about specific molecular pathways involved, and methods for their systematic identification are limited. Here, we developed a forward genetic screening platform that combines CRISPR-Cas9 perturbations, cell coculture picoliter droplets, microfluidic-based fluorescence-activated droplet sorting to identify mechanisms of cell-cell communication. We used SPEAC-seq (systematic...
Abstract Following the present concepts, synthetic sphingosine analog of myriocin FTY720 alters migration and homing lymphocytes via 1-phosphate receptors. However, several studies indicate that immunosuppressive properties may alternatively be due to tolerogenic activities modulation dendritic cell differentiation or based on direct effects CD4+CD25+ regulatory T cells (Treg). As Treg play an important role for cure inflammatory colitis, we used Th1-mediated 2,4,6-trinitrobenzene sulfonic...
It has been reported that retinoic acid (RA) enhances regulatory T (T reg) cell conversion by inhibiting the secretion of cytokines interfere with conversion. This report shows these conclusions provide a partial explanation at best. First, RA not only interfered cytokine but also ability to inhibit reg naive cells. Furthermore, enhanced even in absence inhibitory cytokines. The latter effect depended on receptor α (RARα) did require Smad3, despite fact Smad3 expression. RARα1 isoform was...
Type 1 diabetes (T1D) results from the destruction of insulin-secreting pancreatic β cells by autoreactive T cells. Insulin is an essential target autoimmune attack. epitopes recognized diabetogenic cell clones bind poorly to class II I-Ag7 molecules nonobese diabetic (NOD) mice, which in weak agonistic activity peptide MHC complex. Here, we describe a strongly insulin mimetope that effectively converts naive into Foxp3+ regulatory vivo, thereby completely preventing T1D NOD mice. In...
Abstract Immune tolerance is executed partly by Foxp3 + regulatory T (Treg) cells, which suppress autoreactive cells. In autoimmune type 1 diabetes (T1D) impaired promotes destruction of insulin-producing β-cells. The development autoantigen-specific vaccination strategies for Treg-induction and prevention islet autoimmunity in patients still its infancy. Here, using human haematopoietic stem cell-engrafted NSG-HLA-DQ8 transgenic mice, we provide direct evidence vivo . We identify...
Muscle-residing regulatory T cells (Tregs) control local tissue integrity and function. However, the molecular interface connecting Treg-based regulation with muscle function regeneration remains largely unexplored. Here, we show that exercise fosters a stable induction of highly functional muscle-residing Tregs increased expression amphiregulin (Areg), EGFR, ST2. Mechanistically, find mice lacking IL6Rα on (TKO) harbor significant reductions in Treg functionality satellite fibro-adipogenic...
Abstract In type 1 diabetes, the appearance of islet autoantibodies indicates onset autoimmunity, often many years before clinical symptoms arise. While T cells play a major role in destruction pancreatic beta cells, molecular underpinnings promoting aberrant cell activation remain poorly understood. Here, we show that during autoimmunity an miR142-3p/Tet2/Foxp3 axis interferes with efficient induction regulatory (Treg) resulting impaired Treg stability mouse and human. Specifically,...
Tissue regulatory T cells (Tregs) exert pivotal functions in both immune and metabolic regulation, maintaining local tissue homeostasis, integrity, function. Accordingly, Tregs play a crucial role controlling obesity-induced inflammation supporting efficient muscle function repair. Depending on the context, are characterized by unique transcriptomes, growth, survival factors cell receptor (TCR) repertoires. This functional specialization offers potential to selectively target...
The conversion of naive T cells into Treg can be achieved in vivo by delivery antigen under subimmunogenic conditions. Here we have examined several drugs for their ability to enhance the process and found that rapamycin analog everolimus potently enhances interfering with T-cell costimulation, reducing cell division thereby activation DNA methyltransferase 1 as well through ATP-gated P2×7 receptor controlling Ca2 + influx. resulting Tregs exhibit increased stability Foxp3 expression even...
Abstract NFAT transcription factors control T-cell activation and function. Specifically, the factor NFATc2 affects regulation of cell differentiation growth plays a critical role in development colonic inflammation. Here, we used an experimental model colitis-associated colorectal carcinoma to investigate contribution promotion tumors. Compared with wild-type animals that readily presented multiple colon tumors, NFATc2-deficient mice were protected from tumor development. This observed...
A miRNA181a/NFAT5 signaling axis promotes immune activation and interferes with the induction of regulatory T cells in islet autoimmunity.
Significance The onset of type 1 diabetes autoimmunity is indicated by the development multiple islet autoantibodies, produced B cells with help T follicular helper (TFH) cells. MicroRNAs (miRNAs) are small noncoding RNAs that regulate cellular states, as immune activation, making them suitable targets for disease intervention. Here, we show an enrichment insulin-specific C-X-C chemokine receptor 5 (CXCR5) + CD4 TFH precursors correlating high miRNA92a abundance during and identify...
In addition to its well defined role as a key regulator of calcium and bone metabolism, 1,25-dihydroxyvitamin D<sub>3</sub> (calcitriol) has been established potent modulator immune cell function. Still, because the hypercalcemic toxicity occurring after systemic application parent compound, clinical an immunosuppressant hampered. Recently, we described 22-ene-25-oxa-vitamin D (ZK156979) representative novel class low calcemic vitamin analogs with preserved immunosuppressive activity in...
Treating autoimmune diseases without nonspecific immunosuppression remains challenging. To prevent or treat these conditions through targeted immunotherapy, we developed a clinical-stage nanoparticle platform that leverages the tolerogenic capacity of liver sinusoidal endothelial cells (LSECs) to restore antigen-specific immune tolerance. In vivo efficacy was evaluated in various CD4+ T cell-mediated disease models, including preventive and therapeutic models myelin oligodendrocyte...
Abstract The hypothalamus in the central nervous system (CNS) has important functions controlling systemic metabolism. A calorie-rich diet triggers CNS immune activation, impairing metabolic control and promoting obesity Type 2 Diabetes (T2D), but mechanisms driving hypothalamic activation remain unclear. Here we identify regulatory T cells (Tregs) as key modulators of responses. In mice, environments activate CD4 + cells, infiltrating macrophages microglia while reducing Tregs. mRNA...
To compare the anorectic effectiveness of leptin and amylin analogue salmon calcitonin (sCT), rodents were treated on 1 day with subcutaneous injections. In chow‐fed C57Bl/6J mice, sCT reduced energy intake acted additively. After mice had become leptin‐resistant being fed chocolate as a palatable high‐caloric supplement to chow, their sCT‐induced decrease in was more pronounced than differential changes (strong reduction) chow (slight increase). Dose‐response relationships for reductions...