A5010925940- Neuroinflammation and Neurodegeneration Mechanisms
- T-cell and B-cell Immunology
- Calcium signaling and nucleotide metabolism
- Multiple Sclerosis Research Studies
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Immune cells in cancer
- Ion Channels and Receptors
- Chemokine receptors and signaling
- Adenosine and Purinergic Signaling
- Mitochondrial Function and Pathology
- Immune Response and Inflammation
- Bioactive Compounds and Antitumor Agents
- Systemic Lupus Erythematosus Research
- Vagus Nerve Stimulation Research
- MicroRNA in disease regulation
- Metabolism and Genetic Disorders
- RNA Research and Splicing
- Barrier Structure and Function Studies
- Cholesterol and Lipid Metabolism
- Bacterial Infections and Vaccines
- Genetic Neurodegenerative Diseases
- Atherosclerosis and Cardiovascular Diseases
- Neurogenesis and neuroplasticity mechanisms
- Nuclear Receptors and Signaling
Universitätsmedizin Göttingen
2011-2025
University of Göttingen
2009-2022
Hertie Foundation
2009-2015
Max Planck Institute of Experimental Medicine
2014
Max Planck Institute of Neurobiology
2004-2010
Ludwig-Maximilians-Universität München
2010
Medizinische Hochschule Hannover
2010
Aichi Cancer Center
2010
Nagoya Industrial Science Research Institute
2010
University of Bonn
2010
We tracked pathogenic myelin basic protein-specific CD4+ effector T cells in early central nervous system (CNS) lesions of experimental autoimmune encephalomyelitis (EAE) by combining two-photon imaging and fluorescence video microscopy. made two key observations: (a) the majority (65%) moved fast (maximal speed 25 μm/min) apparently nondirected through compact tissue; (b) a second group (35%) appeared tethered to fixed point. Polarization cell receptor adhesion molecules (lymphocyte...
The clinical picture of experimental autoimmune encephalomyelitis (EAE) is critically dependent on the nature target autoantigen and genetic background animals. Potentially lethal EAE mediated by myelin basic protein (MBP)–specific T cells in Lewis rats, whereas transfer S100β- or oligodendrocyte glycoprotein (MOG)–specific causes intense inflammatory response central nervous system (CNS) with minimal disease. However, Dark Agouti pathogenicity MOG-specific resembles one MBP-specific rat....
Alpha-synuclein (aSyn) is a central player in Parkinson's disease (PD) but the precise molecular mechanisms underlying its pathogenicity remain unclear. It has recently been suggested that nuclear aSyn may modulate gene expression, possibly via interactions with DNA. However, biological behavior of nucleus and factors affecting transcriptional role are not known. Here, we investigated aSyn-mediated transcription deregulation by assessing effects impact phosphorylation these dynamics. We...
Abstract Multiple Sclerosis (MS) is an inflammatory demyelinating disorder in which remyelination failure contributes to persistent disability. Cholesterol rate-limiting for myelin biogenesis the developing CNS; however, whether cholesterol insufficiency MS, unclear. Here, we show relationship between cholesterol, myelination and neurological parameters mouse models of demyelination remyelination. In cuprizone model, acute disease reduces serum levels that can be restored by dietary...
Multiple sclerosis (MS) is caused by T cells that are reactive for brain antigens. In experimental autoimmune encephalomyelitis, the animal model MS, myelin-reactive initiate process when entering nervous tissue and become reactivated upon local encounter of their cognate CNS antigen. Thereby, strength T-cellular reactivation within crucial manifestation severity clinical disease. Recently, B were found to participate in pathogenesis autoimmunity, with several diverse underlying mechanisms...
To maintain homeostasis, the body, including brain, reprograms its metabolism in response to altered nutrition or disease. However, consequences of these challenges for energy different brain cell types remain unknown. Here, we generated a proteome atlas major central nervous system (CNS) from young and adult mice, after feeding therapeutically relevant low-carbohydrate, high-fat ketogenic diet (KD) during neuroinflammation. Under steady-state conditions, CNS prefer distinct modes...
The nucleotide NAADP was recently discovered as a second messenger involved in the initiation and propagation of Ca(2+) signaling lymphoma T cells, but its impact on primary cell function is still unknown. An optimized, synthetic, small molecule inhibitor action, termed BZ194, designed synthesized. BZ194 neither interfered with mobilization by d-myo-inositol 1,4,5-trisphosphate or cyclic ADP-ribose nor capacitative entry. specifically effectively blocked NAADP-stimulated [(3)H]ryanodine...
Approximately 80% of neuromyelitis optica spectrum disorder (NMOSD) patients harbor serum anti-aquaporin-4 autoantibodies targeting astrocytes in the CNS. Crucial for NMOSD lesion initiation is disruption blood-brain barrier (BBB), which allows entrance Abs and complement into CNS a target new therapies. Astrocytes have important functions BBB maintenance; however, influence their loss role immune cell infiltration on permeability not yet been investigated. Using an experimental model...
Nicotinic acid adenine dinucleotide phosphate represents a newly identified second messenger in T cells involved antigen receptor-mediated calcium signalling. Its function vivo is, however, unknown due to the lack of biocompatible inhibitors. Using recently developed inhibitor, we explored role nicotinic autoreactive effector during experimental autoimmune encephalomyelitis, animal model for multiple sclerosis. We provide vitro and evidence that signalling controlled by is relevant...
We explored the effect of i.v. soluble antigen on autoaggressive, myelin basic protein-specific effector T cells within their target organ during acute experimental autoimmune encephalomyelitis (EAE). Intravital two-photon imaging revealed that autoantigen reached CNS and was taken up processed by antigen-presenting 30 min after injection. The exogenous dramatically changed motility function autoreactive EAE lesions: had been cruising through tissue slowed down became tethered to local 1 h....
Administration of the CD28 superagonistic antibody JJ316 is an efficient means to treat autoimmune diseases in rats, but humanized TGN1412 caused devastating side effects healthy volunteers during a clinical trial. Here we show that treatment rats induced dramatic redistribution T lymphocytes from periphery secondary lymphoid organs, resulting severe lymphopenia. Live imaging organs revealed administration almost instantaneously (<2 minutes) arrested cells situ. This reduction cell motility...