A5074184764- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Chronic Lymphocytic Leukemia Research
- CAR-T cell therapy research
- Chemokine receptors and signaling
- Phagocytosis and Immune Regulation
- Immunodeficiency and Autoimmune Disorders
- Angiogenesis and VEGF in Cancer
- Lymphoma Diagnosis and Treatment
- Cell Adhesion Molecules Research
- Acute Myeloid Leukemia Research
- Immune Response and Inflammation
- 14-3-3 protein interactions
- Monoclonal and Polyclonal Antibodies Research
- Viral Infectious Diseases and Gene Expression in Insects
- Atherosclerosis and Cardiovascular Diseases
- HER2/EGFR in Cancer Research
- Complement system in diseases
- Virus-based gene therapy research
- Neuroinflammation and Neurodegeneration Mechanisms
- Helicobacter pylori-related gastroenterology studies
- Multiple Myeloma Research and Treatments
- IL-33, ST2, and ILC Pathways
- Lymphatic System and Diseases
Max Delbrück Center
2016-2025
The Pirbright Institute
2006
Freie Universität Berlin
2002
Boston Children's Hospital
1996-1999
Harvard University
1997-1999
Beth Israel Deaconess Hospital
1997
University of Göttingen
1992-1996
Brigham and Women's Hospital
1996
Antigen-pulsed dendritic cells (DCs) are used as natural adjuvants for vaccination, but the factors that influence efficacy of this treatment poorly understood. We investigated parameters affect migration subcutaneously injected mouse-mature DCs to draining lymph node. found efficiency DC varied with number and CCR7+/+ migrating node, not CCR7-/- failed do so, efficiently induced a rapid increase in node cellularity, which was observed before onset T cell proliferation. also report could be...
Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides (AAV) are life-threatening systemic autoimmune diseases manifesting in the kidneys as necrotizing crescentic glomerulonephritis (NCGN). ANCA antigens myeloperoxidase (MPO) or proteinase 3. Current treatments include steroids, cytotoxic drugs and B cell-depleting antibodies. The use of chimeric antigen receptor (CAR) T cells is a promising new therapeutic approach. We tested hypothesis that CAR targeting CD19 deplete...
The formation of intrapulmonary immune complexes in mice generates a vigorous inflammatory response characterized by microvascular permeability and polymorphonuclear neutrophil influx. Gene-targeted disruption the substance P receptor (NK-1R) protected lung from complex injury, as did C5a anaphylatoxin receptor. Immunoreactive was measurable fluids lining at time points before influx may thus be involved an early step to lung.
We recently demonstrated that gene-targeted disruption of the C5a anaphylatoxin receptor prevented lung injury in immune complex–mediated inflammation. In this study, we compare effect C5aR deficiency complex–induced inflammation peritoneal cavity and skin with results derived from our complex alveolitis model. C5aR- deficient mice exhibit decreased migration neutrophils levels TNF-α interleukin 6 reverse passive Arthus reaction compared to their wild-type littermates. was also required for...
Abstract Foxp3 + CD25 CD4 Treg play a fundamental role in the maintenance of self tolerance and control inflammatory reactions. Previous data demonstrated division labor between naive‐ effector/memory‐like subsets, which is largely based on their lymph node‐recirculating inflammation‐seeking migration behavior, respectively. The chemokine receptor CCR7 expressed both types albeit at different levels. Whether it fulfills similar or distinct roles these subsets has not been studied so far. We...
Chimeric antigen receptor (CAR) redirected T cells are potent therapeutic options against hematological malignancies. The current dominant manufacturing approach for CAR depends on retroviral transduction. With the advent of gene editing, insertion a CD19-CAR into cell (TCR) alpha constant (TRAC) locus using adeno-associated viruses transfer was demonstrated, and these showed improved functionality over their retrovirally transduced counterparts. However, clinical-grade production is complex...
Abstract Allogeneic natural killer (NK) cell adoptive transfer is a promising treatment for several cancers but less effective the of multiple myeloma. In this study, we report on quadruple gene-engineered induced pluripotent stem (iPSC)-derived NK cells designed mass production from renewable source and dual targeting against myeloma through introduction an cell-optimized chimeric antigen receptor (CAR) specific B maturation (BCMA) high affinity, non-cleavable CD16 to augment...
The hallmark of pulmonary tuberculosis is the granuloma, which consists predominantly lymphocytes and macrophages promotes immune-cell interaction with causative pathogen, Mycobacterium tuberculosis. Granuloma formation a highly organized process, depends on leukocyte recruitment facilitated by adhesion molecules chemokines. Thus, during chronic experimental tuberculosis, granulomata display characteristics lymphoid structures comprising follicular aggregation B cells, high endothelial...
Drainage of central nervous system (CNS) antigens to the brain-draining cervical lymph nodes (CLN) is likely crucial in initiation and control autoimmune responses during multiple sclerosis (MS). We demonstrate neuronal within CLN MS patients. In monkeys mice with experimental encephalomyelitis (EAE) mouse models non-inflammatory CNS damage, type extent damage was associated frequencies nodes. addition, drained spinal-cord-draining lumbar human CLN, were present pro-inflammatory...
Abstract Objective Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease with unknown etiology and only partially defined pathogenesis. The aim of this study was to establish murine model in which the development tertiary lymphoid tissue, hallmark human RA, locally induced, characterize roles homeostatic chemokine receptors CXCR5 CCR7 process. Methods We developed modified antigen‐induced (AIA) mice strong bias toward inflammation. Disease pathology assessed up 9 months...
In human chronic lymphocytic leukemia (CLL) pathogenesis, B-cell antigen receptor signaling seems important for ontogeny, whereas the microenvironment influences activation, tumor cell lodging, and provision of antigenic stimuli. Using murine Eμ-Tcl1 CLL model, we demonstrate that CXCR5-controlled access to follicular dendritic cells confers proliferative stimuli B cells. Intravital imaging revealed a marginal zone cell-like trafficking route. Murine reciprocally stimulated resident...
The IκB kinase (IKK)-NF-κB pathway is activated as part of the DNA damage response and controls both inflammation resistance to apoptosis. How these distinct functions are achieved remained unknown. We demonstrate here that double-strand breaks elicit two subsequent phases NF-κB activation in vivo vitro, which mechanistically functionally distinct. RNA-sequencing reveals first-phase anti-apoptotic gene expression, while second drives expression senescence-associated secretory phenotype...
Abstract CAR-T cell therapy targeting CD19 demonstrated strong activity against advanced B leukemia, however shows less efficacy lymphoma with nodal dissemination. To target both Non-Hodgkin’s (B-NHLs) and follicular T helper (Tfh) cells in the tumor microenvironment (TME), we apply here a chimeric antigen receptor (CAR) that recognizes human CXCR5 high avidity. CXCR5, physiologically expressed on mature Tfh cells, is also highly B-NHLs. Anti-CXCR5 eradicate B-NHL lymphoma-supportive more...
Abstract The adoptive immune response relies on a precise temporal and spatial positioning of lymphocytes within lymphoid nonlymphoid tissues. Chemokines, constitutively expressed or induced during inflammation provide flexible navigation system directing into specific microcompartments. Precision specificity in this process are achieved by varying patterns chemokine receptors the cell surface course differentiation. CXCR5 CCR7 principal regulators for targeting T cells, B dendritic cells...
Ectopic lymphoid follicles are a key feature of chronic inflammatory autoimmune and infectious diseases, such as rheumatoid arthritis, Sjögren's syndrome, Helicobacter pylori-induced gastritis. Homeostatic chemokines considered to be involved in the formation tertiary tissue. High expression CXCL13 its receptor, CXCR5, has been associated with ectopic diseases. Here, we defined role CXCR5 development mucosal tissue gastric inflammation mouse model H. pylori infection. CXCR5-deficient mice...
Infection with helminths and exposure to antigens induce a strong type 2 immune response resulting in the secretion of cytokines IL-4 IL-13 by CD4(+) T cells several innate cell types. promote class switch recombination IgG1 IgE while their role for germinal center (GC) formation is poorly understood. We found dramatic reduction numbers GC B when investigating different responses IL-4/IL-13-deficient mice. IL-4/IL-13 from located outside B-cell follicles was sufficient formation. further...
Autologous T cells genetically modified with a chimeric antigen receptor (CAR) redirected at CD19 have potent activity in the treatment of B cell leukemia and non-Hodgkin's lymphoma (B-NHL). Immunotherapies to treat multiple myeloma (MM) targeted maturation (BCMA), which is expressed most cases MM. We developed humanized CAR specificity for BCMA based on our previously generated anti-BCMA monoclonal antibody. The targeting single-chain variable fragment (scFv) domain exhibited binding...
Pulmonary alveolar proteinosis (PAP) is a syndrome characterized by accumulation of surfactant lipoproteins within the lung alveoli. Alveolar macrophages (AMs) are crucial for clearance, and their differentiation depends on colony-stimulating factor 2 (CSF2), which regulates establishment an AM-characteristic gene regulatory network. Here, we report that transcription CCAAT/enhancer binding protein β (C/EBPβ) essential development AM identity, as demonstrated transcriptome chromatin...