A5102853222- interferon and immune responses
- Inflammasome and immune disorders
- Systemic Lupus Erythematosus Research
- RNA regulation and disease
- Cytokine Signaling Pathways and Interactions
- Immune Response and Inflammation
- Immune Cell Function and Interaction
- RNA Research and Splicing
- Immunodeficiency and Autoimmune Disorders
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- RNA modifications and cancer
- Bone Tissue Engineering Materials
- T-cell and B-cell Immunology
- Inflammatory Myopathies and Dermatomyositis
- Collagen: Extraction and Characterization
- Neurogenetic and Muscular Disorders Research
- Inflammatory Bowel Disease
- Advanced biosensing and bioanalysis techniques
- Phosphorus and nutrient management
- Skin Diseases and Diabetes
- Genomics and Chromatin Dynamics
- Monoclonal and Polyclonal Antibodies Research
- Food Industry and Aquatic Biology
- Long-Term Effects of COVID-19
- Nitrogen and Sulfur Effects on Brassica
TU Dresden
2015-2024
University Hospital Carl Gustav Carus
2014-2024
Helmholtz Zentrum München
2010-2022
Klinikum rechts der Isar
2021
Technical University of Munich
2021
University of Tübingen
2019
Heinrich Heine University Düsseldorf
2017
Deutsches Diabetes-Zentrum e.V.
2017
German Center for Diabetes Research
2017
Klinik und Poliklinik für Kinder- und Jugendmedizin
2017
Familial chilblain lupus is a monogenic form of cutaneous erythematosus caused by loss-of-function mutations in the nucleases TREX1 or SAMHD1. In family without SAMHD1 mutation, we sought to determine causative gene and underlying disease pathology. Exome sequencing was used for identification. Structural analysis performed homology modelling docking simulations. Type I interferon (IFN) activation assessed cells transfected with STING cDNA using an IFN-β reporter Western blotting. IFN...
Genome integrity is continuously challenged by the DNA damage that arises during normal cell metabolism. Biallelic mutations in genes encoding genome surveillance enzyme ribonuclease H2 (RNase H2) cause Aicardi-Goutières syndrome (AGS), a pediatric disorder shares features with autoimmune disease systemic lupus erythematosus (SLE). Here we determined heterozygous parents of AGS patients exhibit an intermediate phenotype and demonstrated genetic association between rare RNASEH2 sequence...
UNC93B1 is critical for trafficking and function of nucleic acid-sensing Toll-like receptors (TLRs) TLR3, TLR7, TLR8, TLR9, which are essential antiviral immunity. Overactive TLR7 signaling induced by recognition self-nucleic acids has been implicated in systemic lupus erythematosus (SLE). Here, we report variants (E92G R336L) four patients with early-onset SLE. Patient cells or mouse macrophages carrying the produced high amounts TNF-α IL-6 upon stimulation TLR7/TLR8 agonist, but not TLR3...
Hyperactive TLR7 signaling has long been appreciated as driver of autoimmune disease in mouse models. Recently, gain-of-function mutations were identified a monogenic cause human lupus. is an intracellular transmembrane receptor, sensing RNA breakdown products within late endosomes. Here, we show that endosome dysfunction leads to unrestricted and associated with The endosomal BORC complex together the small GTPase Arl8b controls levels by regulating receptor turnover. This requires direct...
The initial contact of osteoblasts with implant surfaces is an important event for osseointegration implants. Osseointegration Ti6Al4V may be improved by precoating its surface collagen type I. In this study, the adhesion rat calvarial to uncoated and I-coated titanium alloy was investigated over a period 24 h. Collagen I-coating accelerates in presence fetal calf serum. One hour after plating, no differences percentage adherent cells between were found. Adhesion reduced GRGDSP peptide about...
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.
Abstract Immune recognition of cytosolic DNA represents a central antiviral defence mechanism. Within the host, short single-stranded (ssDNA) continuously arises during repair damage induced by endogenous and environmental genotoxic stress. Here we show that ssDNA traverses nuclear membrane, but is drawn into nucleus binding to replication factors RPA Rad51. Knockdown Rad51 enhances leakage resulting in cGAS-dependent type I IFN activation. Mutations exonuclease TREX1 cause IFN-dependent...
<h3>Importance</h3> Familial chilblain lupus is a monogenic autosomal dominant form of cutaneous erythematosus that in most cases caused by mutations the 3 prime repair exonuclease 1 (<i>TREX1</i>). presents early childhood with cold-induced painful erythematous infiltrates leading to mutilation and associated systemic involvement illustrated an elevated type I interferon (IFN) signature skin blood. Effective treatment currently not available. <h3>Objectives</h3> To evaluate clinical...
Familial chilblain lupus is a rare, autosomal dominant form of erythematosus characterized by cold-induced inflammatory lesions at acral locations presenting in early childhood. usually caused mutation TREX1 (3' repair exonuclease 1).We report on family with segregating novel (c.585C>G; H195Q) within the highly conserved (Exo) III domain. Affected members experienced varying degrees, ranging from bluish-red infiltrations to mutilating necrotic ulcerations. In addition, all patients showed...
The RNase Regnase-1 is a master RNA regulator in macrophages and T cells that degrades cellular viral upon NF-κB signaling. roles of its family members, however, remain largely unknown. Here, we analyzed Regnase-3-deficient mice, which develop hypertrophic lymph nodes. We used various mice with immune cell-specific deletions Regnase-3 to demonstrate acts specifically within myeloid cells. deficiency systemically increased IFN signaling, the proportion immature B innate cells, suppressed...
Cutaneous lupus erythematosus (CLE), the main manifestation of systemic (SLE), is driven by type I interferons (IFNs) and often only partially responds to conventional therapies. Treatment seven SLE patients with monoclonal antibody anifrolumab induced fast sustained remission previously refractory CLE lesions, beginning within first weeks treatment. Decline in CLASI-A score was paralleled a reduction IFN determined mRNA expression IFN-stimulated genes (ISGs) blood. These data suggest that...
Spondyloenchondrodysplasia (SPENCD) is a rare skeletal dysplasia, characterized by metaphyseal lesions, neurological impairment and immune dysregulation associated with lupus-like features. SPENCD caused biallelic mutations in the ACP5 gene encoding tartrate-resistant phosphatase. We report on child, who presented spasticity, multisystem inflammation, autoimmunity immunodeficiency minimal changes due to compound heterozygosity for two novel mutations. These findings extend phenotypic...
Background Inborn errors of immunity (IEI) present with a large phenotypic spectrum disease, which can pose diagnostic and therapeutic challenges. Suppressor cytokine signaling 1 (SOCS1) is key negative regulator signaling, has recently been associated novel IEI. Of patients described to date, it apparent that SOCS1 haploinsufficiency pleiotropic effect in humans. Objective We sought investigate whether dysregulation immune pathways, addition STAT1, play role the broad clinical...
Abstract Bcl-3 is an atypical NF-κB family member that regulates NF-κB-dependent gene expression in effector T cells, but a cell-intrinsic function regulatory (Treg) cells and colitis not clear. Here we show levels colonic correlate with disease manifestation patients inflammatory bowel disease. Mice T-cell-specific overexpression of develop severe can be attributed to defective Treg cell development function, leading the infiltration immune such as pro-inflammatory γδT αβ cells. In...
Abstract Background STING-associated vasculopathy with onset in infancy (SAVI) is a rare type I interferonopathy caused by heterozygous variants the STING gene. In SAVI, confer gain-of-function which causes overactivation of interferon (IFN) signaling leading to autoinflammation and various degrees immunodeficiency autoimmunity. Case presentation We report case 5 year old child his mother, both whom presented systemic inflammatory symptoms yet widely varying organ involvement, disease course...
STAT3-hyper IgE syndrome (STAT3-HIES) is a primary immunodeficiency presenting with destructive lung disease along other symptoms. CRISPR-Cas9-mediated adenine base editors (ABEs) have the potential to correct one of most common STAT3-HIES causing heterozygous STAT3 mutations (c.1144C>T/p.R382W). As proof-of-concept, we successfully applied ABEs p.R382W in patient fibroblasts and induced pluripotent stem cells (iPSCs). Treated showed correction efficiency 29% ± 7% without detectable...