- Immune Response and Inflammation
- IL-33, ST2, and ILC Pathways
- Immune cells in cancer
- Inflammatory Bowel Disease
- Autoimmune and Inflammatory Disorders Research
- Ocular Diseases and Behçet’s Syndrome
- Inflammasome and immune disorders
- Systemic Lupus Erythematosus Research
- Immunotherapy and Immune Responses
- S100 Proteins and Annexins
- Advanced Glycation End Products research
- Cytokine Signaling Pathways and Interactions
- Immune Cell Function and Interaction
- Neonatal Respiratory Health Research
- Reproductive System and Pregnancy
- Microscopic Colitis
- Monoclonal and Polyclonal Antibodies Research
- Immunodeficiency and Autoimmune Disorders
- Neonatal and Maternal Infections
- Inflammation biomarkers and pathways
- Acute Kidney Injury Research
- Renal Diseases and Glomerulopathies
- Lymphoma Diagnosis and Treatment
- Preterm Birth and Chorioamnionitis
- Sepsis Diagnosis and Treatment
University Hospital Münster
2013-2021
University of Münster
2011-2020
University of Göttingen
2011-2014
Uniwersytecki Szpital Dziecięcy
2014
Children's Clinical University Hospital
2014
Hertie Foundation
2014
Temple Street Children's University Hospital
2014
Boston Children's Hospital
2013
Institute of Immunology
2011
Targeting the surface of malignant cells has evolved into a cornerstone in cancer therapy, paradigmatically introduced by success humoral immunotherapy against CD20 lymphoma. However, tumor cell susceptibility to immunochemotherapy varies, with mostly fatal outcome cases resistant disease. Here, we show that lymphoma exosomes shield target from antibody attack and exosome biogenesis is modulated lysosome-related organelle-associated ATP-binding cassette (ABC) transporter A3 (ABCA3). B-cell...
S100A12 is overexpressed during inflammation and a marker of inflammatory disease. Furthermore, it has been ascribed to the group damage-associated molecular pattern molecules that promote inflammation. However, exact role human early steps immune activation sepsis only partially described thus far.We analyzed monocytes by granulocyte-derived as key function processes development sepsis.Circulating was determined in patients with healthy subjects experimental endotoxemia. The release from...
Objective Systemic‐onset juvenile idiopathic arthritis (JIA) is speculated to follow a biphasic course, with an initial systemic disease phase driven by innate immune mechanisms and interleukin‐1β (IL‐1β) as key cytokine second chronic arthritic that may be dominated adaptive immunity cytokines such IL‐17A. Although recent mouse model points critical role of IL‐17–expressing γ/δ T cells in pathology, humans, both the prevalence IL‐17 IL‐17–producing are still unclear. Methods Serum samples...
Whether earlier initiation of RRT in critically ill patients with AKI can improve outcomes remains debated. We examined follow-up data from a large clinical trial to prospectively investigate the long-term associated timing such patients. extended Early Versus Delayed Initiation Critically Ill Patients (ELAIN) Trial 90 days 1 year after randomization for 230 (99.6%) The primary outcome was composite major adverse kidney events (persistent renal dysfunction, dialysis dependence, and...
Human and murine studies showed that GM-CSF exerts beneficial effects in intestinal inflammation. To explore whether mediates its via monocytes, we analyzed of on monocytes vitro assessed the immunomodulatory potential GM-CSF-activated (GMaMs) vivo. We used microarray technology functional assays to characterize GMaMs a mouse model colitis study GMaM functions activates increase adherence, migration, chemotaxis, oxidative burst vitro, primes monocyte response secondary microbial stimuli. In...
Objective Monosodium urate monohydrate (MSU) crystal–induced interleukin‐1β (IL‐1β) secretion is a critical factor in the pathogenesis of gout. However, without costimulation by proIL‐1β–inducing factor, MSU crystals alone are insufficient to induce IL‐1β secretion. The responsible costimulatory factors that act as priming endogenous signal vivo not yet known. We undertook this study analyze properties myeloid‐related protein 8 (MRP‐8) and MRP‐14 (endogenous Toll‐like receptor 4 [TLR‐4]...
Rationale: IL-18 is a member of the IL-1 cytokine family, and elevated blood concentrations associate with disease activity in macrophage activation syndrome (MAS) poor clinical outcomes severe inflammatory septic conditions.Objectives: Although recent investigations provide mechanistic evidence for contribution to inflammation hyperinflammation sepsis MAS, we sought study regulatory mechanisms underlying human expression.Methods: Samples from vivo vitro endotoxin rechallenge experiments,...
Abstract Crohn's disease (CD) and ulcerative colitis (UC) have a chronic-remittent course. Optimal management of inflammatory bowel diseases (IBD) relies on early intervention, treat-to-target strategies tight control. However, it is challenging to assess the risk relapses in individual patients. We investigated blood-based biomarkers for confirmation remission patients with IBD. retrospectively analyzed samples 40 IBD (30 UC, 10 CD) enrolled tight-control follow-up study. Half had flare...
The receptor for advanced glycation end products (RAGE) is involved in innate immune mechanisms. Polymorphisms of the RAGE gene have been described as a factor amplifying inflammation susceptible patients, but association with Crohn's disease (CD) not known. coding polymorphism G82S (rs2070600) and two promoter polymorphisms, -374T/A (rs1800624) -429T/C (rs1800625), were studied samples from Germany United States consisting 421 317 CD patients 549 218 controls, respectively. To test...
Familial Mediterranean fever (FMF) is an autoinflammatory disorder caused by pyrin-encoding MEFV mutations. Patients present with recurrent but self-limiting episodes of acute inflammation and often have persistent subclinical inflammation. The pathophysiology only partially understood, neutrophil overactivation a hallmark the disease. S100A12 neutrophil-derived proinflammatory danger signal that strongly elevated in active FMF. This study was undertaken to characterize secretory activity...
Abstract The LIM and SH3 domain protein 1 (Lasp1) was originally cloned from metastatic breast cancer characterised as an adaptor molecule associated with tumourigenesis cell invasion. However, the regulation of Lasp1 its function in aggressive transformation cells is unclear. Here we use integrative epigenomic profiling invasive fibroblast-like synoviocytes (FLS) patients rheumatoid arthritis (RA) mouse models disease, to identify epigenomically co-modified region chronic inflammatory a...
Recent developments suggest a causal link between inflammation and impaired bacterial clearance in Crohn's disease (CD) due to alterations of intestinal macrophages. Studies that excessive is the consequence an underlying immunodeficiency rather than primary cause CD pathogenesis. We characterized phenotypic functional features peripheral blood monocytes patients with quiescent (n = 18) healthy controls 19) by analyses cell surface molecule expression, adherence, migration, chemotaxis,...
The inhibition of Janus kinases (JAKs) and subsequent signal transducers activators transcription (STATs) by tofacitinib represents a new therapeutic strategy in inflammatory bowel diseases (IBD) as clinical trials have led to approval for ulcerative colitis (UC) hint at possible efficacy Crohn`s disease (CD). However, the impact on cellular response monocytes, which are key players responses, has not been investigated so far. We aimed analyze JAK/STAT-inhibition monocytes IBD patients...
Background. The receptor for advanced glycation end products (RAGE) is a multiligand involved in number of processes and disorders. While it known that RAGE-signaling can contribute to toxic liver damage fibrosis, its role acute inflammatory injury septic multiorgan failure yet undefined. We examined RAGE lipopolysaccharide (LPS) induced D-galN sensitized mice as classical model tumor necrosis factor alpha (TNF-α) dependent organ damage. Methods. Mice (Rage-/- C57BL/6) were intraperitoneally...
The interactions of fibroblast-like synoviocyte (FLS)-derived pro-inflammatory cytokines/chemokines and immune cells support the recruitment activation inflammatory in RA. Here, we show for first time that classical myokine myostatin (GDF-8) is involved Th17 to sites thereby regulating joint inflammation a mouse model TNFalpha-mediated chronic arthritis. Mechanistically, myostatin-deficiency leads decreased levels chemokine CCL20 which associated with less infiltration into inflamed joints....
Glucocorticoids (GCs) are used as first-line therapies for generalized suppression of inflammation (e.g., allergies or autoimmune diseases), but their long-term use is limited by severe side effects. Our previous work revealed that GCs induced a stable anti-inflammatory phenotype in monocytes, the GC-stimulated monocytes (GCsMs) we exploited targeted GC-mediated therapeutic We demonstrate GCsMs interact with T cells suppressing proliferation, well cytokine release CD8(+) and, especially,...
Granulocyte macrophage colony-stimulating factor (GM-CSF) treatment induces clinical response in patients with active Crohn's disease. To explore whether monocytes mediate GM-CSF effects vivo, we used a mouse model of chronic colitis induced by dextran sulfate sodium (DSS).Murine bone marrow-derived were activated vitro, and gene expression, phenotype, function GM-CSF-activated (GMaM) analyzed. Therapeutic GMaM assessed repeated cycles DSS. Monocytes administered intravenously their...
Introduction: Sepsis has a grave impact on neonatal morbidity and mortality. Proper timely diagnosis subsequently tailored management are crucial to improving outcome survival. New diagnostic methods needed much effort is directed this objective. In work, we aimed evaluate S100A12 protein as biomarker of sepsis.Materials methods: prospective single-center study, 118 preterm term neonates were enrolled assigned four groups: controls, infants with no infection, probable infection proven...
Glucocorticoids (GCs) constitute a highly pleiotropic class of drugs predominantly employed in the treatment inflammatory diseases. In our search for new mechanisms action, we identified hitherto unknown effect GCs gastrointestinal tract. We found that oral administration dexamethasone (Dex) to mice caused an enlargement stomach due induction gastroparesis and this was abolished GR(dim) carrying A458T mutation GC receptor (GR). Gastroparesis unrelated enhanced gastric acid secretion observed...
Abstract Background The Janus kinase/signal transducer and activator of transcription (JAK/STAT) inhibitor tofacitinib has been recently approved for the treatment ulcerative colitis (UC) but not Crohn’s disease (CD). Systematic analysis JAK/STAT pathway in inflammatory bowel is still missing. aim this study was to investigate activation adjacent signaling monocytes patients with diseases, which are key players responses. Methods Blood samples active UC (n = 28) CD healthy controls 22) were...
Purpose: To characterize peripheral blood T cells in juvenile idiopathic arthritis-associated uveitis (JIAU). Methods: Blood samples were taken from children with JIAU (n = 18), JIA without ocular involvement 11), anterior (IAU, n 12), and healthy controls 11). Cells stained for cell surface markers, intracellular cytokine staining was performed after stimulation analyzed by flow cytometry. Results: The Th1/Th2 ratio increased patients. Numbers of IL-13-expressing an level IL-13 IL-10...