A5081503278- T-cell and B-cell Immunology
- Complement system in diseases
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- Invertebrate Immune Response Mechanisms
- Systemic Lupus Erythematosus Research
- Blood Coagulation and Thrombosis Mechanisms
- Trypanosoma species research and implications
- Single-cell and spatial transcriptomics
- Immune cells in cancer
- Immune Response and Inflammation
- Platelet Disorders and Treatments
- interferon and immune responses
- Ubiquitin and proteasome pathways
- Virus-based gene therapy research
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Glycosylation and Glycoproteins Research
- Peptidase Inhibition and Analysis
- RNA Interference and Gene Delivery
- Mosquito-borne diseases and control
- Phagocytosis and Immune Regulation
- Blood groups and transfusion
- Immunodeficiency and Autoimmune Disorders
- Congenital heart defects research
Aarhus University
2015-2025
Boston Children's Hospital
2010-2018
Harvard University
2010-2017
Aarhus University Hospital
2010
Essential effector functions of innate immunity are mediated by complement activation initiated soluble pattern recognition molecules: mannan-binding lectin (MBL) and the ficolins. We present a novel, phylogenetically conserved protein, MAp44, which is found in human serum at 1.4 microg/ml Ca(2+)-dependent complexes with molecules. The affinity for MBL nanomolar range (K(D) = 0.6 nM) as determined surface plasmon resonance. first eight exons gene MAp44 encode four domains shared...
Abstract The lectin pathway of complement is an important component innate immunity. Its activation has been thought to occur via recognition pathogens by mannan-binding (MBL) or ficolins in complex with MBL-associated serine protease (MASP)-2, followed MASP-2 autoactivation and cleavage C4 C2 generating the C3 convertase. MASP-1 MASP-3 are related proteases found similar complexes. shown aid convertase generation auxiliary cleavage. In mice, have reported be central also alternative...
The pattern-recognition molecules mannan-binding lectin (MBL) and the three ficolins circulate in blood complexes with MBL-associated serine proteases (MASPs). When MBL or ficolin recognizes a microorganism, activation of MASPs occurs leading to complement system, an important component innate immune system. Three proteins are produced from MASP1 gene: MASP-1 MASP-3 MAp44. We present assay specific for MASP-1, which is based on inhibition binding anti-MASP-1-specific antibody domains coated...
Significance A salient feature of the immune system is its ability to discriminate self from nonself. We define molecular mechanism governing activation an ancient and central component: lectin pathway complement. The basis association two proteases in distinct complexes with at least five pattern recognition molecules. Clustering these on ligand surfaces allows cross-activation proteases, which subsequently activate downstream factors initiate a proteolytic cascade. This conceptually...
Antigen binding by B cell receptors (BCR) on cognate cells elicits a response that eventually leads to production of antibodies. However, it is unclear what the distribution BCRs naïve and how antigen triggers first step in BCR signaling. Using DNA-PAINT super-resolution microscopy, we find most are present as monomers, dimers, or loosely associated clusters resting cells, with nearest-neighbor inter-Fab distance 20-30 nm. We leverage Holliday junction nanoscaffold engineer monodisperse...
Abstract Mannan-binding lectin-associated serine protease 2 (MASP-2) is an enzyme of the innate immune system. MASP-2 forms complexes with pattern recognition molecules mannan-binding lectin (MBL), H-ficolin, L-ficolin, or M-ficolin, and activated when one these proteins recognizes microorganisms subsequently cleaves complement factors C4 C2, thus initiating activation Missense polymorphisms exist in different ethnic populations. To further characterize nature these, we have produced...
Abstract The lectin pathway of complement is an integral component innate immunity. It activated upon binding mannan-binding (MBL) or ficolins (H-, L-, and M-ficolin) to suitable ligand patterns on microorganisms. MBL are polydisperse homo-oligomeric molecules, found in complexes with MBL-associated serine proteases (MASP-1, -2, -3) proteins (MAp19 MAp44). This scenario far more complex than the well-defined activation classical pathway, C1qC1r2C1s2, composition activating ill defined. We...
The factors that allow self‐reactive B cells to escape negative selection and become activated remain poorly defined. Using a BCR knock‐in mouse strain, we identify pathway by which ‐cell nucleolar self‐antigens is complement dependent. Deficiency in component C 4 led breakdown the elimination of autoreactive clones at transitional stage, characterized relative increase their response range stimuli, entrance into follicles, greater propensity form GC s. mixed BM chimeras, found myeloid...
Follicular dendritic cells (FDCs), a rare and enigmatic stromal cell type in the B follicles of secondary lymphoid organs, store present antigen to cells. While essential for germinal center (GC) responses, their exact role during GC selection remains unknown. FDCs upregulate inhibitory IgG Fc receptor FcγRIIB formation. We show that deficiency does not affect frequencies compared wild-type mice. However, absence on FDCs, GCs aberrant autoreactive selective foreign responses. These are more...
Introduction Many autoimmune diseases are characterized by germinal center (GC)-derived, affinity-matured, class-switched autoantibodies, and strategies to block GC formation progression currently being explored clinically. However, extrafollicular responses can also play a role. The aim of this study was investigate the contribution pathway disease development. Methods We blocked knocking out transcription factor Bcl-6 in B cells, leaving intact. tested impact intervention two murine models...
Abstract Circumstantial evidence suggests that B cells may instruct T to break tolerance. Here, test this hypothesis, we used a murine model in which single cell clone precipitates an autoreactive response resembling systemic lupus erythematosus (SLE). The initiating did not need enter germinal centers precipitate epitope spreading. Rather, it localized extrafollicular splenic bridging channels early the response. Autoantibody produced by was sufficient drive Subsequent spreading depended on...
Mitochondria, the powerhouses of our cells, are remnants a eubacterial endosymbiont. Notwithstanding evolutionary time that has passed since initial endosymbiotic event, mitochondria have retained many hallmarks their origin. Recent studies indicated during perturbations normal homeostasis, such as following acute trauma leading to massive necrosis and release mitochondria, immune system might mistake symbiont for enemy initiate an inappropriate response. The innate is first line defense...