A5019684451- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- IL-33, ST2, and ILC Pathways
- CAR-T cell therapy research
- Toxoplasma gondii Research Studies
- Neuroinflammation and Neurodegeneration Mechanisms
- Gut microbiota and health
- Cancer Immunotherapy and Biomarkers
- Immune cells in cancer
- Neuroscience and Neuropharmacology Research
- Immune Response and Inflammation
- Tryptophan and brain disorders
- Immunodeficiency and Autoimmune Disorders
- Reproductive System and Pregnancy
- Signaling Pathways in Disease
- Pregnancy and preeclampsia studies
- Receptor Mechanisms and Signaling
- Neuroblastoma Research and Treatments
- Acute Lymphoblastic Leukemia research
- Digestive system and related health
- Parasitic Infections and Diagnostics
- Cytomegalovirus and herpesvirus research
- T-cell and Retrovirus Studies
- Toxin Mechanisms and Immunotoxins
Otto-von-Guericke University Magdeburg
2013-2024
Charité - Universitätsmedizin Berlin
2010-2016
Klinikum Magdeburg
2015
University Hospital Magdeburg
2015
German Cancer Research Center
2004-2012
Heidelberg University
2004-2012
Technical University of Darmstadt
2007
Max Planck Society
2007
DKFZ-ZMBH Alliance
2005
Max Planck Institute for Brain Research
2005
Tumor neovasculature substantially derives from sprouting of existing vessels, whereas the functional contribution bone marrow-derived progenitors to neovessels remains controversial. We used transgenic mouse models multistep carcinogenesis monitor incorporation cells into and elucidate mechanisms endothelial precursor cell (EPC) recruitment tumor microenvironment. unequivocally demonstrate integration marrow vasculature as a late event in that temporally correlates with VEGF release by...
Efficient expression of genes transferred by retroviral vectors is a prerequisite for gene therapy, especially when the biological effect depends on amount transgene product. High-level desirable several therapy approaches involving T lymphocytes. We evaluated standard with cis-regulatory control elements Moloney murine leukemia virus (Mo-MLV) or without human cell-specific CD2 enhancer. For comparison, containing long terminal repeat (LTR) myeloproliferative sarcoma (MPSV) and an improved...
It is widely accepted that cellular immune responses are induced by CD4+ T helper 1 (Th1) cells secreting interleukin (IL)-2 and interferon (IFN)-γ. Tumor immunity often mediated cytotoxic lymphocytes (CTLs) whose activation supported Th1 cytokines. Since IL-4 directs Th2 development has been shown to inhibit Th1-dominated responses, we assumed IL-4–deficient (IL-4−/−) mice would develop vigorous CTL-mediated tumor compared with IL-4–competent (IL-4+/+) mice. Surprisingly, IL-4−/− were...
The stroma of solid tumors is a complex network different cell types. We analyzed interactions in two tumor models during cyclophosphamide (Cy)-induced rejection. In growing tumors, infiltrating macrophages (TIMs) produced interleukin (IL)-10. Beginning 6 h after Cy-treatment T cells the were inactivated and TIMs switched to interferon (IFN)-γ production. Both, IL-10 production before IFN-γ by required cells. With same kinetics as started produce vasculature was destroyed which receptor...
IL-7 is a major regulator of lymphocyte homeostasis; however, little known about the mechanisms that regulate production. To study Il7 gene regulation in vivo, we generated novel IL-7-reporter mouse, which allows non-invasive quantification activity live mice and, additionally, simultaneous activation/inactivation target genes IL-7-producing cells. With these mice, identify thymus, skin and intestine as sources vivo. Importantly, show IFN-gamma commensal microflora promote steady-state...
Abstract Healthy, nonimmunized C57BL/6 (B6) mice contain memory phenotype CD8+ T cells, which are assumed to be generated in response environmental Ags. Since neonatal functionally lymphopenic within the first days after birth, we investigated alternative possibility that cells of untreated B6 result lymphopenia-induced proliferation during life. We show here adoptively transferred proliferate mice, rapidly produce IFN-γ, and develop into maintained until adulthood. In contrast CD4+ was IL-7...
N-Methyl-d-aspartate (NMDA) receptors are tetrameric protein complexes composed of the glycine-binding NR1 subunit with a glutamate-binding NR2 and/or NR3 subunit. Tri-heteromeric containing NR1, NR2, and subunits reconstitute channels, which differ strikingly in many properties from respective glycine- glutamate-gated NR1/NR2 NR1/NR3 gated by glycine alone. Therefore, an accurate oligomerization process different has to assure proper NMDA receptor assembly, been assumed occur via...
Cerebral infections are restrained by a complex interplay of tissue-resident and recruited peripheral immune cells. Whether innate lymphoid cells (ILCs) involved in the orchestration neuroinflammatory dynamics is not fully understood. Here, we demonstrate that ILCs accumulate cerebral parenchyma, choroid plexus, meninges onset Toxoplasma gondii infection. Antibody-mediated depletion conventional natural killer (cNK) ILC1s early stage infection results diminished cytokine chemokine expression...
Toxoplasma gondii (T. gondii) is a highly successful parasite being able to cross all biological barriers of the body, finally reaching central nervous system (CNS). Previous studies have highlighted critical involvement blood-brain barrier (BBB) during T. invasion and development subsequent neuroinflammation. Still, potential contribution choroid plexus (CP), main structure forming blood-cerebrospinal fluid (CSF) (BCSFB) not been addressed.To investigate at onset neuroinflammation, CP brain...
IFN-gamma regulates multiple processes in the immune system. Although its antimicrobial effector functions are well described, less is known about mechanisms by which CD8(+) T cell homeostasis. With help of adoptive transfers, we show this study that IFN-gammaR signaling cells dispensable for expansion, contraction, and memory differentiation response to peptide vaccination. In contrast, host counterregulates responses generation processes, partially regulated CD11b(+) cells. Similar...
B cells are important effectors and regulators of adaptive innate immune responses, inflammation autoimmunity, for instance in anti-NMDA-receptor (NMDAR) encephalitis. Thus, pharmacological modulation B-cell function could be an effective regimen therapeutic strategies. Since the non-competitive NMDAR antagonist memantine is clinically applied to treat advanced Alzheimer`s disease ketamine supposed improve course resistant depression, it know how these drugs affect function. Non-competitive...
Cerebral toxoplasmosis is characterized by activation of brain resident cells and recruitment specific immune cell subsets from the periphery to central nervous system (CNS). Our studies revealed that rapidly invaded Ly6G+ neutrophil granulocytes are an early non-lymphoid source interferon- (IFN-) γ, cytokine known be major mediator host resistance Toxoplasma gondii (T. gondii). Upon selective depletion neutrophils, we detected reduced IFN-γ production increased parasite burden in CNS....
Abstract The survival of peripheral T cells is dependent on their access to LNs (pLNs) and stimulation by IL‐7. In pLNs fibroblastic reticular (FRCs) lymphatic endothelial (LECs) produce IL‐7 suggesting contribution the IL‐7‐dependent cells. However, production detectable in multiple organs not restricted pLNs. This raises question whether pLN‐derived required for maintenance cell homeostasis. Here, we show that numbers naive (T N ) remain unaffected spleen mice lacking Il7 gene activity pLN...
Abstract CD8+ effector T cells recognize malignant by monitoring their surface for the presence of tumor-derived peptides bound to MHC class I molecules. In addition, Ags can be cross-presented APCs. IFN-γ production is often critical tumor rejection. However, it remained unclear whether 1) secrete in response Ag recognition on or APCs and 2) mediates its antitumor effect acting host cells. We show this study that reject tumors bone marrow-chimeric mice incapable cross-presenting...
Activation of tumor-associated CD8+ cytotoxic T lymphocytes (CTLs) often requires antigen representation, e.g., by dendritic cells (DCs), and CD4+ cell help. Previously, we showed that CTL-mediated tumor immunity required interleukin 4 (IL-4) during the immunization but not effector phase. To determine source target IL-4, performed adoptive transfers using from IL-4−/− IL-4R−/− mice analyzed CTL generation. Even though necessary for generation, did need to express IL-4 or IL-4R....
Abstract IFN-γ has a dual function in the regulation of T cell homeostasis. It promotes expansion effector cells and simultaneously programs their contraction. The cellular mechanisms leading to this functional dichotomy have not been identified date. In study we show: 1) that wild-type CD8+ is defective IFN-γ-deficient mice but increased IFN-γR-deficient mice; 2) contraction pool impaired both mouse strains. Furthermore, show CD11b+ responding are sufficient limit promote data presented...
Interleukin-7 (IL-7) is a major survival factor for mature T cells. Therefore, the degree of IL-7 availability determines size peripheral cell pool and regulates homeostasis. Here we provide evidence that also homeostasis intestinal epithelial cells (IEC), colon function composition commensal microflora. In cell-deficient, lymphopenic mice, IL-7-producing IEC accumulate. hyperplasia can be blocked by IL-7-consuming or inactivation IL-7/IL-7R signaling pathway. However, blockade pathway...
Abstract In response to primary Ag contact, naive mouse CD8+ T cells undergo clonal expansion and differentiate into effector cells. After pathogen clearance, most die, only a small number of memory cell precursors (TMPs) survive form pool long-lived (TMs). Although high- low-affinity clones are recruited the response, TM consists mainly high-affinity clones. It remains unclear whether more efficient and/or cell-intrinsic processes exclude from pool. this article, we show that lack IFN-γR...
Intrauterine growth restriction (IUGR) is a serious pregnancy complication with short- and long-term health consequences. The mechanisms underlying this condition are not well understood. Animal models the basis for understanding causes of IUGR developing useful therapeutic strategies. Here, we aimed to ascertain in utero fetuses from NK (natural killer cells)/MC (mast cells)-deficient mothers that give birth growth-restricted pups determine time point at which starts. We used high frequency...
It has become increasingly evident that the immune and nervous systems are closely intertwined, relying on one another during regular homeostatic conditions. Prolonged states of imbalance between neural homeostasis, such as chronic neuroinflammation, associated with a higher risk for damage. Toxoplasma gondii is highly successful neurotropic parasite causing persistent subclinical which psychiatric neurodegenerative disorders. Little known, however, by what means neuroinflammation impairment...