A5074085110- Monoclonal and Polyclonal Antibodies Research
- T-cell and B-cell Immunology
- Glycosylation and Glycoproteins Research
- Immune Cell Function and Interaction
- Cytokine Signaling Pathways and Interactions
- Immune Response and Inflammation
- Immunotherapy and Immune Responses
- SARS-CoV-2 and COVID-19 Research
- Allergic Rhinitis and Sensitization
- Blood groups and transfusion
- COVID-19 Clinical Research Studies
- Food Allergy and Anaphylaxis Research
- Long-Term Effects of COVID-19
- Immunodeficiency and Autoimmune Disorders
- Asthma and respiratory diseases
- Galectins and Cancer Biology
- Metabolomics and Mass Spectrometry Studies
- NF-κB Signaling Pathways
- Urticaria and Related Conditions
- Toxin Mechanisms and Immunotoxins
- Diabetes and associated disorders
- COVID-19 epidemiological studies
- Complement system in diseases
- HER2/EGFR in Cancer Research
- Celiac Disease Research and Management
University of Lübeck
2016-2025
University Hospital Schleswig-Holstein
2022-2025
German Center for Lung Research
2018-2024
German Rheumatism Research Centre
2006-2020
Leibniz Association
2012-2018
University of Göttingen
2017
Albany Medical Center Hospital
2014
Institute for Integrative and Experimental Genomics
2011
Rockefeller University
2005-2006
Robert Bosch (Germany)
2006
Lymphocytes circulate through lymph nodes (LN) in search for antigen what is believed to be a continuous process. Here, we show that lymphocyte migration and occurred non-continuous, circadian manner. Lymphocyte homing peaked at night onset, with cells leaving the tissue during day. This resulted strong oscillations cellularity efferent lymphatic fluid. Using lineage-specific genetic ablation of clock function, demonstrated this dependent on rhythmic expression promigratory factors...
Loss of tolerance in systemic lupus erythematosus (SLE) leads to the generation autoantibodies, which accumulate end-organs where they induce disease. Here we show that immunoglobulin (Ig)G2a and 2b autoantibodies are pathogenic isotypes by recruiting FcγRIV expressing macrophages. Class switching, but not development, IgM anti-self B cells these subclasses requires innate immune receptor Toll-like (TLR)9 MyD88 signaling. In their absence, switching autoreactive IgG2a is blocked, resulting...
Background The new types of mRNA-containing lipid nanoparticle vaccines BNT162b2 and mRNA-1273 the adenovirus-based vaccine AZD1222 were developed against SARS-CoV-2 code for its spike (S) protein. Several studies have investigated short-term antibody (Ab) responses after vaccination. Objective However, impact these formats with unclear effects on long-term Ab response – including isotype, subclass, their type Fc glycosylation is less explored. Methods Here, we analyzed anti-S in blood serum...
Interleukin 6 (IL-6) is considered an important mediator of acute inflammatory responses. Moreover, IL-6 functions as a differentiation and growth factor hematopoietic precursor cells, B T keratinocytes, neuronal osteoclasts, endothelial cells. exhibits its action via receptor complex consisting specific (IL-6R) signal transducing subunit (gp130). Soluble forms both components are generated by shedding found in patients with various diseases such acquired immune deficiency syndrome,...
The final differentiation or maturation of dendritic cells (DCs) in response to environmental stimuli influences their ability both initiate immunity and determine the quality antigens. Circulating immune complexes cell-bound immunoglobulins present normal human sera represent a potential stimulus for inadvertent DC activation steady state during autoimmunity. Here, we show that selective blockade inhibitory Fcγ receptor (FcγR) FcγRIIb with recently developed monoclonal antibodies leads...
Antigen-specific Abs are able to enhance or suppress immune responses depending on the receptors that they bind cells. Recent studies have shown pro- antiinflammatory effector functions of IgG also regulated through their Fc N-linked glycosylation patterns. agalactosylated (non-galactosylated) and asialylated proinflammatory induced by combination T cell-dependent (TD) protein antigens costimulation. Sialylated Abs, which immunosuppressive, Tregs produced in presence TD under tolerance...
Abnormalities in expression levels of the IgG inhibitory Fc gamma receptor IIB (FcγRIIB) are associated with development immunoglobulin (Ig) G serum autoantibodies and systemic autoimmunity mice humans. We used Ig gene cloning from single isolated B cells to examine checkpoints that regulate autoreactive germinal center (GC) plasma FcγRIIB-deficient mice. found loss FcγRIIB was an increase poly- IgG+ GC cells, including hallmark anti-nuclear antibody–expressing possess characteristic...
IgG antibodies mediate their effector functions through the interaction with Fcgamma receptors and complement factors. The main IgG-mediated activation pathway is induced binding of C1q to antibodies. This dependent on antigen-dependent hexamer formation human IgG1 IgG3 increase affinity for six-headed molecule. In contrast, IgG4 fails bind C1q. Instead, it has been suggested that can block hexamerization required activating complement. Here, we show murine IgG1, which functionally resembles...
<h3>Objective</h3> Pancreatic autoantibodies (PABs), comprising antibodies against glycoprotein 2 (anti-GP2), are typically associated with complicated phenotypes in Crohn9s disease, but have also been observed variable frequencies patients UC. In a previous study, we high frequency of primary sclerosing cholangitis (PSC) anti-GP2-positive We therefore aimed to characterise the role anti-GP2 PSC. <h3>Design</h3> an evaluation phase, sera from 138 well-characterised Norwegian PSC were...
Pro- and anti-inflammatory effector functions of IgG antibodies (Abs) depend on their subclass Fc glycosylation pattern. Accumulation non-galactosylated (agalactosylated; G0) Abs in the serum rheumatoid arthritis (RA) systemic lupus erythematosus (SLE) patients reflects severity diseases. In contrast, sialylated are responsible for effects intravenous immunoglobulin (IVIG; pooled human from healthy donors), administered high doses (2 g/kg) to treat autoimmune patients. However, whether low...
BackgroundEffector functions of IgG Abs are regulated by their Fc N-glycosylation pattern. glycans that lack galactose and terminal sialic acid residues correlate with the severity inflammatory (auto)immune disorders have also been linked to protection against viral infection discussed in context vaccine-induced protection. In contrast, sialylated shown immunosuppressive effects.ObjectiveWe sought investigate glycosylation programming during germinal center (GC) reaction following...
Afucosylated IgG1 responses have only been found against membrane-embedded epitopes, including anti-S in SARS-CoV-2 infections. These responses, intrinsically protective through enhanced FcγRIIIa binding, can also trigger exacerbated pro-inflammatory severe COVID-19. We investigated if the BNT162b2 mRNA induced afucosylated IgG responses.Blood from vaccinees during first vaccination wave was collected. Liquid chromatography-Mass spectrometry (LC-MS) used to study Fc glycoprofiles....
Recently, it has been questioned whether vaccination of patients with inflammatory (auto)immune diseases under anti-tumor necrosis factor (TNF) treatment leads to impaired vaccine-induced immune responses and protection against breakthrough infections. However, the effects TNF blockade on short- long-term after repeated remain unclear. Vaccination studies have shown that initial short-term IgG antibodies (Abs) carry highly galactosylated sialylated Fc glycans, whilst Abs low levels...
Abstract During thymic T cell development, immature CD4+CD8+ double-positive (DP) thymocytes develop either into CD4+CD8− Th cells or CD4−CD8+ CTLs. Differentially expressed primary factors inducing the fate of these types are still poorly described. The transcription factor Runx3/AML-2 Runx, rust dominant factor; AML, acute myeloid leukemia is specifically during development CD8 single-positive (SP) thymocytes, where it silences CD4 expression. Deletion murine Runx3 results in a reduction...
Abstract The pleiotropic cytokine IL-6 has been predicted to be a protein with four antiparallel alpha-helices. Human acts on human and murine cells, whereas is only active cells. construction of set chimeric human/murine proteins recently allowed us define new region (residues Lys41-Glu95) within the molecule as being important for receptor binding biologic activity. We subdivided analyzed this region, which primarily corresponds loop between first second alpha-helix respect its role in...
Abstract The persistence of CD4 expression is a key event distinguishing the differentiation MHC class II-restricted thymocytes into T cells from that I-restricted CD8 cells. zinc finger transcription factor Zbtb7b (or cKrox or Thpok) normally expressed in and promotes lineage choice. When cells, redirects these their normal fate to differentiation, implying it promotes, directly not, sustained expression; present study has investigated mechanism this effect. We demonstrate that, although...
Coronavirus disease 2019 (COVID-19) is a viral infection affecting multiple organ systems of great significance for metabolic processes. Thus, there increasing interest in and lipoprotein signatures the disease, early analyses have demonstrated pattern typical atherosclerotic hepatic damage COVID-19 patients. However, it remains unclear whether this specific observed signature caused by or rather represents an underlying risk factor. To answer question, we analyzed 482 serum samples using...