A5008846661- Autoimmune Bullous Skin Diseases
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Urticaria and Related Conditions
- Mast cells and histamine
- Skin and Cellular Biology Research
- Phytochemical compounds biological activities
- IgG4-Related and Inflammatory Diseases
- Pancreatitis Pathology and Treatment
- Neuroendocrine Tumor Research Advances
- Autoimmune and Inflammatory Disorders
- T-cell and B-cell Immunology
- Monoclonal and Polyclonal Antibodies Research
- Atherosclerosis and Cardiovascular Diseases
- Liver Diseases and Immunity
- Cell Adhesion Molecules Research
- Food Allergy and Anaphylaxis Research
- Celiac Disease Research and Management
University of Lübeck
2015-2024
Research Center Borstel - Leibniz Lung Center
2015
German Center for Lung Research
2015
Pemphigoid diseases refer to a group of severe autoimmune skin blistering characterized by subepidermal and loss dermal-epidermal adhesion induced autoantibody immune cell infiltrate at the junction upper dermis. Here, we explore role cell-secreted serine protease, granzyme B, in pemphigoid disease pathogenesis using three independent murine models. In all models, B knockout or topical pharmacological inhibition significantly reduces total area compared controls. vivo vitro studies show that...
Regulatory T cells (Tregs) are well known for their modulatory functions in adaptive immunity. Through regulation of cell functions, Tregs have also been demonstrated to indirectly curb myeloid cell-driven inflammation. However, direct effects on insufficiently characterized, especially the context cell-mediated diseases, such as pemphigoid diseases (PDs). PDs caused by autoantibodies targeting structural proteins skin. Autoantibody binding triggers activation through specific Fc gamma...
Abstract T cells are key players in autoimmune diseases by supporting the production of autoantibodies. However, their contribution to effector phase antibody-mediated dermatoses, i.e., tissue injury and inflammation skin, has not been investigated. In this paper, we demonstrate that amplify development autoantibody-induced a prototypical, organ-specific disease, namely epidermolysis bullosa acquisita (EBA) – characterized caused autoantibodies targeting type VII collagen. Specifically, show...
Epidermolysis bullosa acquisita (EBA) is a difficult-to-treat subepidermal autoimmune blistering skin disease (AIBD) with circulating and tissue-bound anti-type VII collagen antibodies. Different reports have indicated increased concentration of tumor necrosis factor α (TNF) in the serum blister fluid patients AIBD. Furthermore, successful anti-TNF treatment has been reported for individual Here we show that mice, induction experimental EBA by repeated injections rabbit anti-mouse type...
Because of the morbidity and limited therapeutic options autoimmune diseases, there is a high, thus far, unmet medical need for development novel treatments. Pemphigoid such as epidermolysis bullosa acquisita (EBA), are prototypical diseases that caused by autoantibodies targeting structural proteins skin, leading to inflammation, mediated myeloid cells. To identify treatment targets, we performed cutaneous genome-wide mRNA expression profiling in 190 outbred mice after EBA induction....
Abstract Pemphigoid diseases (PDs) are a group of autoimmune bullous characterized and caused by autoantibodies targeting structural proteins the skin mucous membranes. Chronic inflammation, subepidermal blistering, often scaring clinical characteristics PDs. Itching and, in severe cases, disabilities resulting from (i.e., blindness, esophageal strictures) leading subjective symptoms. Treatment PDs, which is based on nonspecific immunosuppression, challenging because frequent relapses, lack...
The role of mast cells (MCs) in autoimmunity is the matter an intensive scientific debate. Based on observations different MC-deficient mouse strains, MCs are considered as fundamental players autoimmune diseases. However, most recent data suggest that outcome such diseases strongly affected by individual strain used. By use two c-Kit mutant strains and one c-Kit-independent strain, we here investigated a systemic Ab transfer model epidermolysis bullosa acquisita, subepidermal blistering...
Epidermolysis bullosa acquisita (EBA) is a rare, but prototypical, organ-specific autoimmune disease, characterized and caused by autoantibodies against type VII collagen (COL7). Mucocutaneous inflammation, blistering, scarring are the clinical hallmarks of disease. Treatment EBA difficult mainly relies on general immunosuppression. Hence, novel treatment options urgently needed. The phosphatidylinositol-3-kinase (PI3K) pathway putative target for inflammatory diseases, including EBA. We...
Pemphigus and pemphigoid diseases are characterized caused predominantly by IgG autoantibodies targeting structural proteins of the skin. Their current treatment relies on general prolonged immunosuppression that causes severe adverse events, including death. Hence, novel safe more effective treatments urgently needed. Due to its' physiological functions, neonatal Fc receptor (FcRn) has emerged as a potential therapeutic target for pemphigus pemphigoid, primarily because is protected from...
Pemphigus is caused by autoantibodies against desmoglein (Dsg) 1, Dsg3, and/or non-Dsg antigens. vulgaris (PV) the most common manifestation of pemphigus, with painful erosions on mucous membranes. In cases, blistering also occurs skin, leading to areas extensive denudation. Despite improvements in pemphigus treatment, time achieve remission long, severe adverse events are frequent and 20% patients do not respond adequately. Current clinical developments focus exclusively modulating B cell...
Abstract Genetic studies have added to the understanding of complex diseases. Here, we used a combined genetic approach for risk‐loci identification in prototypic, organ‐specific, autoimmune disease, namely experimental epidermolysis bullosa acquisita ( EBA ), which autoantibodies type VII collagen COL7 ) and neutrophil activation cause mucocutaneous blisters. Anti‐ IgG induced moderate blistering most inbred mouse strains, while some showed severe disease or were completely protected. Using...
Class I phosphoinositide 3-kinases (PI3K) have been implemented in pathogenesis of experimental epidermolysis bullosa acquisita (EBA), an autoimmune skin disease caused by type VII collagen (COL7) autoantibodies. Mechanistically, inhibition specific PI3K isoforms, namely PI3Kβ or PI3Kδ, impaired immune complex (IC)-induced neutrophil activation, a key prerequisite for EBA pathogenesis. Data unrelated to showed that activation is also modulated PI3Kα and γ, but their impact on the has, so...
Chronic blistering at the skin and/or mucous membranes, accompanied by a varying degree of inflammation, is clinical hallmark pemphigoid diseases that impose major medical burden. Pemphigoid are caused autoantibodies targeting structural proteins epithelial basement membrane. One pathogenic pathway and inflammation activation myeloid cells following Fc gamma receptor-dependent binding to skin-bound immune complexes. This process requires specific kinases, such as PI3Kδ, which have emerged...
(1) Background: Autoimmune pancreatitis (AIP) is mainly treated with steroids. Using an AIP mouse model, we investigated two potential alternatives, the transforming growth factor-β-activated kinase 1 inhibitor, takinib, and Janus tofacitinib. (2) Methods: In a multicenter preclinical study, MRL/MpJ mice were injected polyinosinic/polycytidylic acid (poly I:C) for weeks to induce AIP. They then four either takinib (25, 50, or 75 mg/kg body weight), tofacitinib (5, 10 15 mg/kg), dexamethasone...
Abstract EBA is a chronic inflammatory, mucocutaneous blistering skin diseases caused by autoantibodies against the structural protein, COL7. induction requires autoantibody binding as well complement- and Fcγ receptor (FcγR)-dependent inflammation. Using mouse models of EBA, we evaluated: (1) in IgG1-deficient mice, whether preventing production IgG1 anti-COL7 Ab (IgG1 has limited ability to activate complement or FcγRs), influences induced COL7/adjuvant immunization (active model); (2) mAb...