A5053272780- interferon and immune responses
- Inflammasome and immune disorders
- Viral Infections and Vectors
- RNA modifications and cancer
- Autoimmune and Inflammatory Disorders Research
- Mosquito-borne diseases and control
- Cytomegalovirus and herpesvirus research
- Immune Response and Inflammation
- RNA regulation and disease
- Immune Cell Function and Interaction
- Endoplasmic Reticulum Stress and Disease
- Immunodeficiency and Autoimmune Disorders
- Dermatology and Skin Diseases
- NF-κB Signaling Pathways
- Kawasaki Disease and Coronary Complications
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Viral Infections and Outbreaks Research
- Asthma and respiratory diseases
- Cell death mechanisms and regulation
- Paraoxonase enzyme and polymorphisms
- Ocular Diseases and Behçet’s Syndrome
- Exercise and Physiological Responses
- Phagocytosis and Immune Regulation
- Extracellular vesicles in disease
- RNA and protein synthesis mechanisms
University Hospital Carl Gustav Carus
2015-2025
Technische Universität Dresden
2015-2025
Klinik und Poliklinik für Kinder- und Jugendmedizin
2014
The HIV restriction factor, SAMHD1 (SAM domain and HD domain-containing protein 1), is a triphosphohydrolase that degrades deoxyribonucleoside triphosphates (dNTPs). Mutations in cause Aicardi-Goutières syndrome (AGS), an inflammatory disorder shares phenotypic similarity with systemic lupus erythematosus, including activation of antiviral type 1 interferon (IFN). To further define the pathomechanisms underlying autoimmunity AGS due to mutations, we investigated physiological properties SAMHD1.
Stimulator of interferon genes (STING) is activated after detection cytoplasmic dsDNA by cGAS (cyclic GMP-AMP synthase) as part the innate immunity defence against viral pathogens. STING binds TANK-binding kinase 1 (TBK1). TBK1 mutations are associated with familial amyotrophic lateral sclerosis, and pathway has been implicated in pathogenesis further neurodegenerative diseases. To test whether activation sufficient to induce neurodegeneration, we analysed a mouse model that expresses...
The pathophysiological origin of juvenile idiopathic arthritis (JIA) is largely unknown. However, individuals with presumably pathogenic mutations in FAMIN have been reported, associating this gene a rare subtype disorder. FAMIN, that formerly also referred to as LACC1 or C13orf31, has recently shown play crucial role immune-metabolic functions and involved regulation inflammasome activation promotion ROS production. We describe two siblings severe familial forms which whole-exome-sequencing...
Constitutive activation of STING by gain-of-function mutations triggers manifestation the systemic autoinflammatory disease STING-associated vasculopathy with onset in infancy (SAVI). In order to investigate role signaling tumor necrosis factor (TNF) SAVI, we used genetic inactivation TNF receptors 1 and 2 murine which is characterized T cell lymphopenia, inflammatory lung neurodegeneration. Genetic TNFR1 TNFR2, however, rescued loss thymocytes, reduced interstitial Furthermore, TNFR2...
Autoimmune vasculitis is a group of life-threatening diseases, whose underlying pathogenic mechanisms are incompletely understood, hampering development targeted therapies. Here, we demonstrate that patients suffering from anti-neutrophil cytoplasmic antibodies (ANCA)-associated (AAV) showed increased levels cGAMP and enhanced IFN-I signature. To identify disease potential therapeutic targets, developed mouse model for pulmonary AAV mimics severe in patients. Immunogenic DNA accumulated...
Pro-inflammatory caspase-1 is a key player in innate immunity. Caspase-1 processes interleukin (IL)-1β and IL-18 to their mature forms triggers pyroptosis. These functions are linked its enzymatic activity. However, loss-of-function missense mutations CASP1 do not prevent autoinflammation patients, despite decreased IL-1β production. In vitro data suggest that enzymatically inactive drives inflammation via enhanced nuclear factor κB (NF-κB) activation, independent of processing. Here, we...
STING gain-of-function causes autoimmunity and immunodeficiency in mice STING-associated vasculopathy with onset infancy (SAVI) humans. Here, we report that prevents development of lymph nodes Peyer's patches. We show the absence secondary lymphoid organs is associated diminished numbers innate cells (ILCs), including tissue inducer (LTi) cells. Although wild-type (WT) α4β7+ progenitors differentiate efficiently into LTi cells, do not. Furthermore, impairs all types ILCs. Patients mutations...
Caspase-1 (Interleukin-1 Converting Enzyme, ICE) is a proinflammatory enzyme that plays pivotal roles in innate immunity and many inflammatory conditions such as periodic fever syndromes gout. Inflammation often mediated by enzymatic activation of interleukin (IL)-1β IL-18. We detected seven naturally occurring human CASP1 variants with different effects on protein structure, expression, activity. Most mutations destabilized the caspase-1 dimer interface revealed crystal structure analysis...
Abstract The proinflammatory enzyme caspase-1 plays an important role in the innate immune system and is involved a variety of inflammatory conditions. Rare naturally occurring human variants gene (CASP1) lead to different protein expression structure decreased or absent enzymatic activity. Paradoxically, significant number patients with such suffer from febrile episodes despite IL-1β production secretion. In this study, we investigate how variant (pro)caspase-1 can possibly contribute...
The immune response to pathogens or injury relies on the concerted release of cytokines and proteins with biological activity important for host protection, defense, wound healing. Consequently, secretome cells provides a promising resource discovery specific molecular markers targets pharmacological intervention. Here, we employ label-free MS unbiased, quantitative profiling human monocytic cell under different proinflammatory stimuli. profiles reveal highly stimulus-dependent cellular...
Genome damage is a main driver of malignant transformation, but it also induces aberrant inflammation via the cGAS/STING DNA-sensing pathway. Activation can trigger cell death and senescence, thereby potentially eliminating genome-damaged cells preventing against transformation. Here, we report that defective ribonucleotide excision repair (RER) in hematopoietic system caused genome instability with concomitant activation axis compromised stem function, ultimately resulting leukemogenesis....
Background Heterozygous point mutations in the GT splice donor consensus sequence of exon 11 PIK3R1 gene (coding for p85α, p55α, and p50α regulatory subunits PI3K) lead to skipping thereby an aberrant protein that leaves PI3K hyperactivated. Several patients with this particular variant PI3 kinase delta syndrome (APDS) suffering from sinopulmonary infections lymphoproliferation have been described. Methods (Whole exome) sequencing, evaluation cellular clinical phenotypes. Results We here...
Abstract Autoimmune vasculitis is a group of life-threatening diseases, whose underlying pathogenic mechanisms are incompletely understood, hampering development targeted therapies. Here, we demonstrate that patients suffering from anti-neutrophil cytoplasmic antibodies (ANCA)-associated (AAV) showed increased activity the DNA sensor cGAS and enhanced IFN-I signature. To identify potential therapeutic targets, developed mouse model for pulmonary AAV mimics severe disease in patients....
Abstract Constitutive activation of STING by gain-of-function mutations triggers manifestation the systemic autoinflammatory disease STING-associated vasculopathy with onset in infancy (SAVI). In order to investigate role signaling tumor necrosis factor (TNF) SAVI, we used pharmacological inhibition and genetic inactivation TNF receptors 1 2 murine which is characterized T cell lymphopenia, inflammatory lung neurodegeneration. Pharmacologic improved but had no effect on interstitial disease....
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