A5030251740- interferon and immune responses
- Viral Infections and Vectors
- Inflammasome and immune disorders
- Lysosomal Storage Disorders Research
- Renal Diseases and Glomerulopathies
- Immune Response and Inflammation
- Immune Cell Function and Interaction
- Biomedical Research and Pathophysiology
- Cytokine Signaling Pathways and Interactions
- Lipid metabolism and biosynthesis
- RNA regulation and disease
- Diabetes and associated disorders
- Metabolism, Diabetes, and Cancer
- Platelet Disorders and Treatments
- Glycogen Storage Diseases and Myoclonus
- Microtubule and mitosis dynamics
- Mosquito-borne diseases and control
- Herpesvirus Infections and Treatments
- vaccines and immunoinformatics approaches
- Systemic Lupus Erythematosus Research
- Endoplasmic Reticulum Stress and Disease
- Cellular transport and secretion
- Extracellular vesicles in disease
- Biochemical effects in animals
- Health and Wellbeing Research
Aarhus University
2012-2021
Institute for Biomedicine
2011
Abstract Innate immune activation by macrophages is an essential part of host defence against infection. Cytosolic recognition microbial DNA in leads to induction interferons and cytokines through cyclic GMP-AMP synthase (cGAS) stimulator interferon genes (STING). Other factors, including interferon-gamma inducible factor 16 (IFI16), have been proposed contribute DNA. However, their relation the cGAS-STING pathway not clear. Here, we show that IFI16 functions on two distinct levels....
Varicella zoster virus (VZV) typically causes chickenpox upon primary infection. In rare cases, VZV can give rise to life-threatening disease in otherwise healthy people, but the immunological basis for this remains unexplained. We report 4 cases of acute severe infection affecting central nervous system or lungs unrelated, children who are heterozygous missense mutations POLR3A (one patient), POLR3C both (two patients). and encode subunits RNA polymerase III. Leukocytes from all patients...
Signaling through stimulator of interferon genes (STING) leads to the production type I interferons (IFN-Is) and inflammatory cytokines. A gain-of-function mutation in STING was identified an autoinflammatory disease (STING-associated vasculopathy with onset infancy; SAVI). The expression cyclic GMP-AMP, DNA-activated cGAS-STING pathway, increased a proportion patients SLE. signaling pathway may be candidate for targeted therapy Here, we demonstrated that disruption ameliorated lupus...
Nucleic acids are potent stimulators of type I interferon (IFN-I) and antiviral defense, but may also promote pathological inflammation. A range diseases characterized by elevated IFN-I, including systemic lupus erythematosus (lupus). The DNA-activated cGAS-STING pathway is a major IFN-I-inducing pathway, activation signaling dependent on trafficking STING from the ER to Golgi.Here we used cell culture systems, mouse model, material patients, explore mode action antagonistic peptide, its...
Injury to the glomerular podocyte is a key mechanism in human disease and repair an important therapeutic target. In Fabry disease, injury caused by intracellular accumulation of globotriaosylceramide. This study identifies three endocytic receptors, mannose 6-phosphate/insulin-like growth II receptor, megalin, sortilin demonstrates their drug delivery capabilities for enzyme replacement therapy. Sortilin, novel α-galactosidase A binding protein, reveals predominant expression but also...
Many different tissues and cell types exhibit regulated secretion of lipoprotein lipase (LPL). However, the sorting LPL in trans Golgi network has not, hitherto, been understood detail. Here, we characterize role SorLA (officially known as SorLA-1 or sortilin-related receptor) intracellular trafficking LPL. We found that bound to under neutral acidic conditions, cells this binding mainly occurred vesicular structures. expression changed subcellular distribution so it became more concentrated...
The bulk of proteins filtered in the glomeruli are reabsorbed proximal tubule by endocytosis mediated two multiligand receptors operating concert, megalin and cubilin. Podocytes can also internalize protein megalin; this was initially reported rat tubular glomerular epithelial cells has recently been demonstrated human podocytes. Cubilin, crucial for albumin reabsorption tubule, not identified cells.In present study, we used immunocytochemistry reverse transcription-polymerase chain reaction...
The LysRS-Ap 4 A axis impairs cGAS-STING pathway activation, delaying nucleic acid-driven innate immune responses.
Prominent vasculopathy in Fabry disease patients is caused by excessive intracellular accumulation of globotriaosylceramide (GL-3) throughout the vascular endothelial cells causing progressive cerebrovascular, cardiac and renal impairments. The lesions lead to myocardial ischemia, atherogenesis, stroke, aneurysm, thrombosis, nephropathy. Hence, injury kidney a key mechanism human glomerular cell repair an important therapeutic target. We investigated uptake α-galactosidase A (α-Gal A) cells,...
Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the GLA gene. Deficiency of α-galactosidase A (α-Gal A) causes intracellular accumulations globotriaosylceramide (GL-3) and related glycosphingolipids all organs, including kidney, often leading to end-stage renal failure. In women with disease, accumulation GL-3 glomerular podocytes other cells induces progressive, proteinuric nephropathy, but not as severe men. Enzyme replacement therapy (ERT) recombinant α-Gal...
Sortilin and sorCS1 [sortilin-related Vps10p (vacuolar protein sorting/targeting 10) domain-containing receptor 1], both members of the Vps10p-D (Vps10p-domain) family, are synthesized as precursor proteins converted into their mature form by enzymatic cleavage a short N-terminal propeptide. SorCS1 does not bind its propeptide, but sortilin is able to just own also that sorCS1. In present study we show propeptide region contains two separate sites for binding only one these removed from...
Abstract SLE (systemic lupus erythematosus) is an autoimmune disease that causes chronic inflammation and leads to fatality if left untreated. Immune complex-mediated type I IFN signaling pathways are one of the mechanisms initiating disease. Signaling through stimulator interferon genes (STING) production inflammatory cytokines. However, role STING in mouse models controversy. Here we demonstrated involving pathogenesis at molecular level. The disruption rescued Fcgr2b -deficient mice....