A5014573710- Proteoglycans and glycosaminoglycans research
- Cell Adhesion Molecules Research
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Peptidase Inhibition and Analysis
- Immune Cell Function and Interaction
- Glycosylation and Glycoproteins Research
- Dermatology and Skin Diseases
- Cancer-related gene regulation
- Viral gastroenteritis research and epidemiology
- Immune Response and Inflammation
- Hair Growth and Disorders
- Salmonella and Campylobacter epidemiology
- Fungal Infections and Studies
- Calcium signaling and nucleotide metabolism
- Hematopoietic Stem Cell Transplantation
- Chemokine receptors and signaling
- PI3K/AKT/mTOR signaling in cancer
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Cellular transport and secretion
- Extracellular vesicles in disease
- Mycotoxins in Agriculture and Food
- Protease and Inhibitor Mechanisms
- Clostridium difficile and Clostridium perfringens research
- Immune cells in cancer
German Cancer Research Center
2000-2024
Heidelberg University
2000-2024
Novartis (Switzerland)
2013
University Hospital Heidelberg
2009
Zero to Three
2008
Hôpital l'Archet
1996-1997
Inserm
1996-1997
Approximately 164,000 deaths yearly are due to shigellosis, primarily in developing countries. Thus, a safe and affordable Shigella vaccine is an important public health priority. The GSK Vaccines Institute for Global Health (GVGH) developed candidate sonnei (1790GAHB) using the Generalized Modules Membrane Antigens (GMMA) technology. paper reports results of 1790GAHB Phase 1 studies healthy European adults.To evaluate safety immunogenicity profiles 1790GAHB, we performed two parallel, phase...
CD44 designates a large family of proteins with considerable structural and functional diversity, which are generated from one gene by alternative splicing. As such, the overexpression variant isoform (CD44v) has been causally related to metastatic spread cancer cells. To study underlying mechanism, stable knockdown clones deletion exon v7 containing isoforms (CD44v(kd)) highly rat adenocarcinoma line BSp73ASML (ASML(wt)) were established. ASML-CD44v(kd) hardly form lung metastases after...
T cell activation is accompanied by actin-mediated receptor clustering and reorganization of lipid rafts. It has been suggested that costimulatory molecules might be involved in these processes. We here provide evidence engagement the adhesion molecule CD44 initiates cytoskeletal rearrangement membrane cells. Cross-linking on a helper line was adhesion, spreading actin bundle formation. These processes were energy dependent required an intact microtubule system. They small GTPase Rac as...
Abstract Induction of a chronic eczema is most efficient therapy for alopecia areata (AA). We had noted reduction in regulatory T cells during AA induction and wondered whether may become recruited or expanded repeated skin sensitization additional account hair regrowth. could not be cured by the transfer CD4+CD25high lymph node from mice repeatedly treated with contact sensitizer. This obviously consequence dominance freshly activated as compared CD4+CD25+ cells. Instead, population...
T cell activation is supposed to require two signals via the TCR and a co-stimulatory molecule. However, signaling cascade of molecules has remained elusive. Here we provide evidence that CD44, which constitutively associated with lck fyn, supports proliferation as well apoptosis mainly, if not exclusively, by enhancing signal transduction TCR/CD3 complex. Antigenic stimulation helper line in presence CD44 receptor globulin was accompanied significant decrease IL-2 production. To evaluate...
The calcium release-activated channel (CRAC) opened in Jurkat cells activated either with CD3 monoclonal antibody or the endoplasmic reticulum Ca2+-ATPase blocker, thapsigargin, is blocked by La3+ an IC50 of 20 nM. Similarly, entry Mn2+, used as a surrogate for Ca2+, also submicromolar concentrations. seems to play its role simply plugging CRAC because this ion does not penetrate cells, demonstrated chelation experiments EGTA. Blocking Ca2+ influx results lack expression CD25, chain...
There is evidence that cell-associated IL-1 alpha supports immune response induction. Here we explored the impact of malignant cell-derived on immunogenicity, induction and tumor-induced immunosuppression using 3-methylcholanthrene-induced fibrosarcoma lines derived from wild-type (wt), alpha-, beta- or IL-1a beta-knockout (IL-1 alpha(-/-), beta(-/-), alphabeta(-/-)) C57BL6 mice. The wt, beta(-/-) alphabeta(-/-) express MHC class I molecules at a high level. do not differ in their...
Analyzing the growth of fibrosarcoma lines derived from IL-1α–, IL-1β–, or IL-1αβ–knockout (−/−) mice in immunocompetent host revealed that tumor-derived IL-1α and IL-1β exert strong opposing effects on immune response induction, which prohibited evaluation a potential impact tumorigenicity. Therefore, vivo IL-1–deficient tumor was evaluated nu/nu compared with vitro characteristics. All grow immunocompromised mice. However, IL-1α−/−β–competent (comp) more aggressively, efficiently induce...
A blockade of CD44 can interfere with haematopoietic and leukemic stem cell homing, the latter being considered as a therapeutic option in haematological malignancies. We here aimed to explore molecular mechanism underlying efficacy anti-CD44. noted that irradiated mice reconstituted bone marrow transplant, anti-CD44 exerts stronger effect on reconstitution than T lymphoma (EL4) growth. Nonetheless, non-reconstituted mouse suffices for prolonged survival EL4-bearing mice, where...
CD44 is involved in leukocyte migration and activation has recently been reported to contribute extravasation by associating with CD49d. We explored whether similar changes activity are seen vivo using murine alopecia areata (AA) as a chronic, organ-related autoimmune disease model system. Expression of the activated, hyaluronan-binding form CD44, CD49d, was elevated draining lymph node cells (LNC) AA-affected mice compared control mice. LNC AA displayed increased motility, proliferative...
Abstract CD44 plays an important role in leukocyte extravasation, which is fortified autoimmune diseases and delayed-type hypersensitivity (DTH) reactions. There additional evidence that distinct isoforms interfere with the extravasation of selective subsets. We wanted to explore this question alopecia areata (AA), a hair-follicle centric disease, chronic eczema. The became interest because AA treated efficiently by topical application contact sensitizer, such mild DTH reaction maintained...
Abstract Regain of immunocompetence after myeloablation and bone marrow cell (BMC) reconstitution essentially depends on T progenitor homing into the thymus intrathymic maturation. CD44 facilitates settlement in is known as a marker. In search for improving regain BMC reconstitution, we explored whether standard (CD44 s) and/or variant isoforms CD44v6 CD44v7 contribute to repopulation thymocyte Antibody-blocking studies cells/mice with targeted deletion CD44v6/7 or revealed that CD44s, but...
Abstract Blockade of CD44v7 was described to cure trinitrobenzene sulfonic acid-induced colitis, a disease not developed by mice with targeted deletion the exon. There evidence for reduction in activation-induced cell death on lamina propria lymphocytes control as compared CD44v7-deficient mice. To elucidate mechanism underlying relative apoptosis resistance CD44v7-competent lymphocytes, T activation and induction were analyzed mesenteric lymph node cells Peyer’s patch CD44v4-v7-transgenic...
The mechanism by which calcium-depleted intracellular stores may trigger an external calcium influx through a release-activated channel was investigated analyzing the effects of several protein tyrosine kinase inhibitors on movements in Jurkat T cells. Tyrphostin A9, inhibitor activity platelet-derived growth factor (PDGF) receptor, dramatically impaired sustained elevation cytosolic concentration, induced either CD3 mAbs, thapsigargin, ionomycin at low (10(-7) M) or passive depletion...
© 1997 Federation of European Biochemical Societies.
Re‐acquisition of immunocompetence after allogeneic bone marrow cell (BMC) transplantation depends on intrathymic maturation the T progenitor cells. We recently reported that CD44 promotes homing into thymus and T‐cell now elucidate molecular mechanisms CD44‐supported thymocyte maturation. Lethally irradiated, tumor‐bearing mice, allogeneically reconstituted with T‐cell‐depleted BMC a small number common lymphoid 2 cells (CLP2) from transgenic (TG) express ratCD44v4‐v7 under Thy1 promoter,...
T cell activation is supposed to require two signals via the TCR and a co-stimulatory molecule.However, signaling cascade of molecules has remained elusive.Here we provide evidence that CD44, which constitutively associated with lck fyn, supports proliferation as well apoptosis mainly, if not exclusively, by enhancing signal transduction TCR/CD3 complex.Antigenic stimulation helper line in presence CD44 receptor globulin was accompanied significant decrease IL-2 production.To evaluate...