A5020671355- T-cell and B-cell Immunology
- Neuroinflammation and Neurodegeneration Mechanisms
- Hormonal and reproductive studies
- Polyomavirus and related diseases
- Immunotherapy and Immune Responses
- Multiple Sclerosis Research Studies
- Cell Adhesion Molecules Research
- Psoriasis: Treatment and Pathogenesis
- Immune Cell Function and Interaction
- Skin Protection and Aging
- Immune Response and Inflammation
- Doping in Sports
- Muscle metabolism and nutrition
- Circadian rhythm and melatonin
- Full-Duplex Wireless Communications
- Immune cells in cancer
- Barrier Structure and Function Studies
- Proteoglycans and glycosaminoglycans research
- Milk Quality and Mastitis in Dairy Cows
- Mast cells and histamine
- Sphingolipid Metabolism and Signaling
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Complement system in diseases
- Exercise and Physiological Responses
- Microbial infections and disease research
German Sport University Cologne
2021-2024
University Hospital Münster
2015-2019
University of Münster
2012-2019
Inserm
2016
Université Toulouse III - Paul Sabatier
2016
Centre Hospitalier Universitaire de Toulouse
2016
Université de Toulouse
2016
Pain and Rehabilitation Medicine
2014
Institute of Neurobiology
2014
Augenstern
2014
The focus of this study is the characterization human T cell blood-brain barrier migration and corresponding molecular trafficking signatures. We examined peripheral blood cerebrospinal fluid immune cells from patients under long-term anti-very late antigen-4 (VLA-4)/natalizumab therapy (LTNT) CNS specimens. LTNT patients' exhibited healthy central-/effector-memory ratios, but lacked CD49d showed enhanced myeloma adhesion molecule (MCAM) expression. led to an increase PSGL-1 expression on...
Environmental conditions (eg, latitude) play a critical role in the susceptibility and severity of many autoimmune disorders, including multiple sclerosis (MS). Here, we investigated mechanisms underlying beneficial effects immune regulatory processes induced skin by moderate ultraviolet B (UVB) radiation on central nervous system (CNS) autoimmunity.Effects UVB light were analyzed murine model CNS autoimmunity (experimental encephalomyelitis). Additionally, patients with relapsing-remitting...
Inhibition of a mitochondrial enzyme during multiple sclerosis treatment modulates antigen-specific T cell responses in an affinity-dependent fashion.
The aim of the study was to analyze John Cunningham virus (JCV) serology in natalizumab-treated patients over time and assess whether they are influenced by natalizumab treatment.German (n = 1,921; 525 longitudinally) French 1,259; 711 were assessed for JCV alongside their therapy with natalizumab.JCV serostatus changed 69 longitudinally followed German (13.1%) 14.8 months. Seroconversion according seen 43 339 initially JCV- (12.7% months; 10.3% per year) 41 243 (16.9% 24 8.5% year). index...
Background: Natalizumab treatment is associated with progressive multifocal leukoencephalopathy (PML) development. Treatment duration, prior immunosuppressant use, and JCV serostatus are currently used for risk stratification, but PML incidence stays high. Anti-JCV antibody index L-selectin (CD62L) have been proposed as additional stratification parameters. Objective: This study aimed at verifying integrating both parameters into one algorithm stratification. Methods: Multicentric,...
Multiple sclerosis (MS) disease risk is associated with reduced sun-exposure. This study assessed the relationship between measures of sun exposure (vitamin D [vitD], latitude) and MS severity in setting two multicenter cohort studies (nNationMS = 946, nBIONAT 990). Additionally, effect-modification by medication photosensitivity-associated MC1R variants was assessed. High serum vitD a score (MSSS), for relapses, lower disability accumulation over time. Low latitude higher vitD, MSSS, fewer...
G protein-coupled receptors are important regulators of cellular signaling processes. Within the large family rhodopsin-like receptors, those binding to biogenic amines form a discrete subgroup. Activation amine leads transient changes intracellular Ca²⁺-([Ca²⁺](i)) or 3',5'-cyclic adenosine monophosphate ([cAMP](i)) concentrations. Both second messengers modulate processes and thereby contribute long-lasting behavioral effects in an organism. In vivo pharmacology has helped reveal...
Although the CNS is immune privileged, continuous search for pathogens and tumours by cells within indispensable. Thus, distinct immune-cell populations also cross blood-brain barrier independently of inflammation/under homeostatic conditions. It was previously shown that effector memory T populate healthy parenchyma in humans and, independently, CCR5-expressing lymphocytes as well CCR5 ligands are enriched patients with multiple sclerosis. Apart from recently described CD8+ tissue-resident...
The nuclear receptor Liver X Receptor (LXR) is a ligand-activated transcription factor that has been implicated in control of chronic inflammation by downregulating pro-inflammatory T cell responses. An impaired function regulatory cells, subset CD4+ cells with crucial role maintaining lymphocytes homeostasis and immune regulation, frequently observed inflammatory diseases. We pharmacological activation LXR not only resulted thorough suppression Th1 Th17 polarization vitro, but also...
Abstract Purpose Inadvertent and/or unknowing exposure to drugs and drug residues has been frequently debated in situations of so-called adverse analytical finding (AAF) the context sports testing programs. Transfer via unprotected intercourse is a conceivable scenario but scientific data authentic case reports are scarce. Herein, investigations into two AAFs with peroxisome proliferator-activated receptor delta (PPARδ) agonist GW1516 reported discussed. Methods To probe for contamination...
Migration of encephalitogenic CD4+ T lymphocytes across the blood-brain barrier is an essential step in pathogenesis multiple sclerosis (MS). We here demonstrate that expression co-stimulatory receptor NKG2D defines a subpopulation cells with elevated levels markers for migration, activation, and cytolytic capacity especially when derived from MS patients. Furthermore, CD4+NKG2D+ produce high proinflammatory IFN-γ IL-17 upon stimulation. promotes to migrate endothelial vitro model barrier....
Lymphocyte adhesion and subsequent trafficking across endothelial barriers are essential steps in various immune-mediated disorders of the CNS, including MS. The molecular mechanisms underlying these processes, however, still unknown. Phospholipase D1 (PLD1), an enzyme that generates phosphatidic acid through hydrolysis phosphatidylcholine additionally yields choline as a product, has been described regulator cell mobility. By using PLD1-deficient mice, we investigated functional...
Objective: Dimethyl fumarate (DMF) is prescribed against relapsing-remitting multiple sclerosis (MS). Here, we investigated the effects of DMF and monomethyl (MMF), its metabolite in vivo, at (inflamed) blood–brain barrier (BBB). Methods: Effects fumaric acid esters were analyzed using primary human brain–derived microvascular endothelial cells (HBMECs) combination with peripheral blood mononuclear (PBMCs) derived from DMF-treated MS patients. Results: MMF-binding to brain endothelium leads...
GPCR expression was intensively studied in bulk cDNA of leukocyte populations, but limited data are available with respect to individual cells. Here, we show a microfluidic-based single-cell analysis primary T cells, myeloid and endothelial cells under naive conditions during experimental autoimmune encephalomyelitis, the mouse model multiple sclerosis. We found that neuroinflammation induces characteristic changes heterogeneity patterning, identify various functionally relevant subgroups...
Natural killer (NK) cells are a subset of cytotoxic lymphocytes that recognize and kill tumor- virus-infected without prior stimulation. Killing target is multistep process including adhesion to cells, formation an immunological synapse, polarization release cytolytic granules. The role distinct potassium channels in this orchestrated still poorly understood. current study reveals addition the voltage-gated KV 1.3 calcium-activated KCa 3.1 channels, human NK also express two-pore domain K2 P...
Integrin α2β1, also known as very late antigen (VLA)-2, is a collagen-binding molecule expressed constitutively on platelets. Vatelizumab, monoclonal antibody targeting the α2 subunit (CD49b) of VLA-2, was recently investigated for its safety and efficacy during Phase 2 clinical study in multiple sclerosis patients, integrin-mediated collagen binding at site inflammation central to number downstream pro-inflammatory events. In course this study, we could show that VLA-2 ex vivo platelets,...
Abstract Rationale An increasing number of adverse analytical findings (AAFs) in routine doping controls has been suspected and debated to presumably result from intimate contact with bodily fluids (including ejaculate), potentially facilitating the transfer prohibited substances. More precisely, possibility drugs being present ejaculate introduced by sexual intercourse into vagina an athlete and, subsequently, control urine samples, was discussed. Methods Two testing strategies determine...
Migration of encephalitogenic CD4 + T lymphocytes across the blood-brain barrier is an essential step in pathogenesis multiple sclerosis (MS).We here demonstrate that expression co-stimulatory receptor NKG2D defines a subpopulation cells with elevated levels markers for migration, activation, and cytolytic capacity especially when derived from MS patients.Furthermore, produce high proinflammatory IFN-γ IL-17 upon stimulation.NKG2D promotes to migrate endothelial vitro model barrier.CD4 are...
Potential scenarios as to the origin of minute amounts banned substances detected in doping control samples have been a much-discussed problem anti-doping analysis recent years. One such debated scenario has contamination female athletes' urine with ejaculate containing agents and/or their metabolites. The aim this work was obtain complementary information on whether relevant concentration ranges are excreted into and which metabolites can be seminal fluid (sf) corresponding blood plasma...
Abstract Because of its influence on carbohydrate metabolism and, at the same time, anti‐catabolic effects, misuse peptide hormone insulin and synthetic analogs is prohibited in sports all times according to regulations World Anti‐Doping Agency (WADA). The biological effects are mediated through binding receptor, which was also found be activated by different peptides structurally largely unrelated insulin. Such insulin‐mimetic or selective‐insulin receptor modulators (SIRMs) represent a...
Exogenous substances, including drugs and chemicals, can transfer into human seminal fluid influence male fertility reproduction. In addition, substances relevant in the context of sports drug testing programs, be transferred urine a female athlete (after unprotected sexual intercourse) trigger so-called Adverse Analytical Finding. Here, question arises as to whether it is possible distinguish analytically between intentional doping offences unintentional contamination by fluid. To this end,...