A5013841622- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immune Response and Inflammation
- Immune cells in cancer
- vaccines and immunoinformatics approaches
- Neuroinflammation and Neurodegeneration Mechanisms
- Parasitic infections in humans and animals
- RNA Interference and Gene Delivery
- Inflammation biomarkers and pathways
- Chemokine receptors and signaling
- Cell Adhesion Molecules Research
- Parasites and Host Interactions
- CAR-T cell therapy research
- Parasitic Infections and Diagnostics
- Cancer Immunotherapy and Biomarkers
- Multiple Myeloma Research and Treatments
- Reproductive System and Pregnancy
- Parkinson's Disease Mechanisms and Treatments
- Immune responses and vaccinations
- Cellular transport and secretion
- Atherosclerosis and Cardiovascular Diseases
- Toxin Mechanisms and Immunotoxins
- Monoclonal and Polyclonal Antibodies Research
- Antimicrobial Peptides and Activities
University of Würzburg
2016-2025
Institute of Virology of the Slovak Academy of Sciences
2013-2020
Maastricht University Medical Centre
2015
Universitätsklinikum Würzburg
2015
Deutsches Herzzentrum München
2015
Joslin Diabetes Center
2015
Harvard University
2015
Universitätsklinikum Erlangen
2002-2011
University of Konstanz
2010
University of Freiburg
2010
Mature dendritic cells (DCs) are believed to induce T cell immunity, whereas immature DCs tolerance. Here we describe that injections of matured with tumor necrosis factor (TNF)-α (TNF/DCs) antigen-specific protection from experimental autoimmune encephalomyelitis (EAE) in mice. Maturation by TNF-α induced high levels major histocompatibility complex class II and costimulatory molecules on DCs, but they remained weak producers proinflammatory cytokines. One injection such TNF/DCs pulsed...
It has been recently demonstrated that regulatory CD4+CD25+ CD45RO+ T cells are present in the peripheral blood of healthy adults and exert function similar to their rodent counterparts. remains difficult understand how small fraction these regulate via direct cell-to-cell contact not secretion immunosuppressive cytokines could mediate strong immune suppression. Here we show human induce long-lasting anergy production interleukin (IL)-10 CD4+CD25− cells. These anergized then suppress...
Dendritic cells (DC) were cultured from mouse bone marrow (BM) progenitors in low concentrations of granulocyte-macrophage colony-stimulating factor (GM-CSF) (GMlo DC) by two different protocols. The phenotype and functional properties these GMlo DC compared to those standard BM-DC cultures generated high GM-CSF (GMhi or plus IL-4 (GMlo/IL-4 DC). An effect on maturation was observed only at but not doses GM-CSF. Compared mature DC, phenotypically immature, weak stimulators allogeneic...
Immune mechanisms are known to control the pathogenesis of atherosclerosis. However, exact role DCs, which essential for priming immune responses, remains elusive. We have shown here that DC-derived chemokine CCL17 is present in advanced human and mouse atherosclerosis CCL17+ DCs accumulate atherosclerotic lesions. In atherosclerosis-prone mice, Ccl17 deficiency entailed a reduction atherosclerosis, was dependent on Tregs. Expression by limited expansion Tregs restricting their maintenance...
Abstract Dendritic cells migrate from the skin to draining lymph nodes. They transport immunogenic MHC-peptide complexes, present them Ag-specific T in areas, and thus generate immunity. Migrating dendritic encounter physical obstacles, such as basement membranes collagen meshwork. Prior work has revealed that matrix metalloproteinase-9 (MMP-9) contributes mouse Langerhans cell migration. In this study, we use human explant culture models further study role of MMPs migration maturation...
Myeloid-derived suppressor cells (MDSC) and DC are major controllers of immune responses against tumors or infections. However, it remains unclear how development MDSC activity both generated from myeloid precursor regulated. Here, we show that the combined treatment BM-derived with LPS plus IFN-gamma inhibited but enhanced functions, such as NO release T-cell suppression. This was not observed by single treatments in vitro. In spleens healthy mice, identified two...
Abstract Macrophages release IFN-γ on combined stimulation with IL-12 and IL-18, but the signaling requirements of this process its regulation by other cytokines are unknown. Here, we demonstrate that STAT4 is indispensable for IL-12/IL-18-induced production mouse peritoneal macrophages. Type 2 NO synthase (NOS2), which previously found to be a prerequisite IL-12-induced in NK cells, was not required these alone already induced expression mRNA, nuclear translocation STAT4, protein,...
Inadequacy of T-cell responses may result in the development tuberculosis (TB). Myeloid-derived suppressor cells (MDSCs) have been described as suppressors function cancer biology and recently several infectious diseases.To explore presence role MDSCs TB.We analyzed surface markers peripheral blood at site disease TB cases patients with lung cancer, asymptomatic tuberculin skin test-positive individuals recent (household) or remote exposure to Mycobacterium (M.tb) uninfected healthy control...
Donor CD4+Foxp3+ regulatory T cells (T reg cells) suppress graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (HCT [allo-HCT]). Current clinical study protocols rely on the ex vivo expansion of donor and their infusion in high numbers. In this study, we present a novel strategy for inhibiting GvHD that is based recipient before allo-HCT, exploiting crucial role tumor necrosis factor receptor 2 (TNFR2) biology. Expanding radiation-resistant host mice...
<h3>Background</h3> Ovarian cancer (OvCA) tissues show abundant expression of the ectonucleotidases CD39 and CD73 which generate immunomodulatory adenosine, thereby inhibiting cytotoxic lymphocytes. Little, however, is known about effect adenosine on myeloid cells. Considering that tumor associated macrophages (TAM) myeloid-derived suppressor cells (MDSC) constitute up to 20 % OvCA tissue, we investigated explored a possible contribution generation in vitro ex vivo. <h3>Methods</h3>...
Abstract Human regulatory macrophages (Mreg) have shown early clinical promise as a cell-based adjunct immunosuppressive therapy in solid organ transplantation. It is hypothesised that recipient CD4 + T cell responses are actively regulated through direct allorecognition of donor-derived Mregs. Here we show human Mregs convert allogeneic cells to IL-10-producing, TIGIT FoxP3 -induced non-specifically suppress bystander and inhibit dendritic maturation. Differentiation Mreg-induced Tregs...
Antigen-specific neuroinflammation and neurodegeneration are characteristic for neuroimmunological diseases. In Parkinson's disease (PD) pathogenesis, α-synuclein is a known culprit. Evidence α-synuclein-specific T cell responses was recently obtained in PD. Still, causative link between these dopaminergic had been lacking. We thus addressed the functional relevance of immune PD mouse model. utilized model which an Adeno-associated Vector 1/2 serotype (AAV1/2) expressing human mutated...
Previous reports have indicated that both dendritic cells and macrophages the ability to induce cytotoxic T lymphocyte (CTL) helper (Th) cell responses in vivo. Dendritic process exogenous antigens conventionally for presentation on major histocompatibility complex (MHC) class II molecules. However, unconventional processing of vitro MHC I molecules is still an open question. In this study, we report a cloned line (D2SC/1) able present debris-associated viral proteins I-restricted CTL vitro....
Abstract Tolerogenic activity of myeloid dendritic cells (DC) has so far been attributed mostly to immature or semi‐mature differentiation stages but never their precursor cells. Although suppressor (MSC) have isolated ex vivo , developmental relationship DC and precise phenotype remained elusive. Here, we describe the generation MSC as precursors with potent suppressive on allogeneic OVA‐specific CD4 + CD8 T cell responses in vitro . These appear transiently cultures bone marrow (BM) after...
CD83 is up-regulated on the surface of dendritic cells (DCs) during maturation and has been widely used as a marker for mature DCs. Recently, we reported recombinant expression extracellular immunoglobulin domain human (hCD83ext). Using this soluble form CD83, allogeneic well specific cytotoxic T lymphocyte proliferation could be blocked in vitro. Here report functional analysis vivo, using murine experimental autoimmune encephalomyelitis (EAE) model. Strikingly, only three injections...
Abstract Little is known about the distinct roles of two types IL-4R on DC. Here we report that IL-4 and IL-13 are able to promote DC maturation, as evaluated by up-regulation MHC class II costimulatory molecules, when concentration GM-CSF relatively lower than dose or IL-13. In addition, under these conditions both cytokines enable respond maturation stimuli such bacterial products proinflammatory cytokines. Both act synergistically with weak TNF-α CD40. The signaling for requires α-chain...
Abstract Skin-draining lymph nodes contain a number of dendritic cell (DC) subsets different origins. Some these are migratory, such as the skin-derived epidermal Langerhans cells and separate dermal DC subset, whereas others lymphoid resident in nature, CD8+ DCs found throughout tissues. In this study, we examine subset presentation self-Ag by migratory lymphoid-resident DCs, both steady state under conditions local skin infection. We show that is confined to migrating settings. Steady...
Background Alveolar echinococcosis, caused by Echinococcus multilocularis larvae, is a chronic disease associated with considerable modulation of the host immune response. Dendritic cells (DC) are key effectors in shaping response and among first encountered parasite during an infection. Although it assumed that E.multilocularis, excretory/secretory (E/S)-products, specifically affects DC to deviate responses, little information available on molecular nature respective E/S-products their...
Abstract The Gr‐1 (RB6‐8C5) Ab binds with high affinity to mouse Ly‐6G molecules and a lower extent Ly‐6C has been widely used for cell depletion in infected or tumor‐bearing mice. Here we found that treatment of BM cells vitro vivo showed no depleting effects. epitope recognized by the overlapped (1A8 Ab) but not (ER‐MP20 Ab). In transmitted signals via STAT‐1, STAT‐3 STAT‐5 into cells, similar GM‐CSF. healthy mice injected Ab, remained attached surface myeloid at least four days. induced...