A5056642802- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Cancer Immunotherapy and Biomarkers
- Asthma and respiratory diseases
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Allergic Rhinitis and Sensitization
- IL-33, ST2, and ILC Pathways
- Gut microbiota and health
- Acute Lymphoblastic Leukemia research
- Cytokine Signaling Pathways and Interactions
- Immune Response and Inflammation
- interferon and immune responses
- Cancer Cells and Metastasis
- Cancer-related gene regulation
- Glioma Diagnosis and Treatment
- Lymphoma Diagnosis and Treatment
- Invertebrate Immune Response Mechanisms
- Epigenetics and DNA Methylation
- Advanced Chemical Sensor Technologies
- Single-cell and spatial transcriptomics
- Probiotics and Fermented Foods
- Clostridium difficile and Clostridium perfringens research
- Marine Invertebrate Physiology and Ecology
- FOXO transcription factor regulation
Philipps University of Marburg
2015-2024
German Rheumatism Research Centre
2021-2024
Institute of Medical Microbiology and Hygiene
2017-2022
Institut für Medizinische Informatik, Biometrie und Epidemiologie
2012
University of Cologne
2005
TU Dresden
2001
Abstract Emerging data demonstrate that the activity of immune cells can be modulated by microbial molecules. Here, we show short-chain fatty acids (SCFAs) pentanoate and butyrate enhance anti-tumor cytotoxic T lymphocytes (CTLs) chimeric antigen receptor (CAR) through metabolic epigenetic reprograming. We in vitro treatment CTLs CAR with increases function mTOR as a central cellular sensor, inhibits class I histone deacetylase activity. This reprogramming results elevated production...
Abstract Short-chain fatty acids (SCFAs) have immunomodulatory effects, but the underlying mechanisms are not well understood. Here we show that pentanoate, a physiologically abundant SCFA, is potent regulator of immunometabolism. Pentanoate induces IL-10 production in lymphocytes by reprogramming their metabolic activity towards elevated glucose oxidation. Mechanistically, this mediated supplying additional pentanoate-originated acetyl-CoA for histone acetyltransferases, and...
Pancreatic ductal adenocarcinoma (PDAC) is characterised by an abundant desmoplastic stroma composed of cancer-associated fibroblasts (CAF) and interspersed immune cells. A non-canonical CD8
Follicular T-helper (T FH ) cells cooperate with GL7 + CD95 germinal center (GC) B to induce antibody maturation. Herein, we identify the transcription factor IRF4 as a T-cell intrinsic precondition for T cell differentiation and GC formation. After immunization protein or infection protozoon Leishmania major , draining lymph nodes (LNs) of IFN-regulatory factor-4 ( Irf4 −/− mice lacked GCs despite developing normal initial hyperplasia. were also absent in Peyer’s patches naive mice....
Immune microenvironment plays a critical role in lung cancer control versus progression and metastasis. In this investigation, we explored the effect of tumor-infiltrating lymphocyte subpopulations on biology by studying vitro cocultures, vivo mouse models, human tissue. Lymphocyte conditioned media (CM) induced epithelial-mesenchymal transition (EMT) migration both primary cells cell lines. Correspondingly, major accumulation Th9 Th17 was detected tissue correlated with poor survival....
IL-17-producing CD8+ (Tc17) cells are enriched in active lesions of patients with multiple sclerosis (MS), suggesting a role the pathogenesis autoimmunity. Here we show that amelioration MS by dimethyl fumarate (DMF), mechanistically elusive drug, associates suppression Tc17 cells. DMF treatment results reduced frequency Tc17, contrary to Th17 cells, and decreased ratio regulators RORC-to-TBX21, along shift towards cytotoxic T lymphocyte gene expression signature from patients....
Abstract Intratumoral cytotoxic CD8+ T cells (CTL) enter a dysfunctional state characterized by expression of coinhibitory receptors, loss effector function, and changes in the transcriptional landscape. Even though several regulators T-cell exhaustion have been identified, molecular mechanisms inducing remain unclear. Here, we show that IL18 receptor (IL18R) signaling induces murine pancreatic cancer model. Adoptive transfer Il18r−/− OT-1 CTLs resulted enhanced rejection subcutaneous tumors...
Robust cytotoxic CD8 + T-cell response is important for immunity to intracellular pathogens. Here, we show that the transcription factor IFN Regulatory Factor 4 (IRF4) crucial protective bacterium Listeria monocytogenes . IRF4-deficient ( Irf4 −/− ) mice could not clear L. infection and generated decreased numbers of -specific T cells with impaired effector phenotype function. Transfer wild-type into improved bacterial clearance, suggesting an intrinsic defect in mice. Following transfer...
Granulocyte-macrophage colony-stimulating factor (GM-CSF) controls proliferation and survival of myeloid cells including monocytes. Here, we describe a time-dependent licensing process driven by GM-CSF in murine Ly6Chigh human CD14+ monocytes that disables their inflammatory functions promotes conversion into suppressor cells. This 2-step requires activation the AKT/mTOR/mTORC1 signaling cascade followed through interferon-γ receptor (IFN-γR)/interferon regulatory factor-1 (IRF-1) pathway....
The accumulation of intratumoral CD8+ T cells is associated with the survival high grade serous ovarian carcinoma patients, but it unclear which cell subsets contribute to this effect and how they are affected by peritoneal tumor microenvironment. Here, we provide evidence for a functional link between long relapse-free survival, effector memory (TEM) in effusion (ascites), level TEM attracting chemokine CXCL9, produced macrophages as major source. We also propose novel mechanism...
Alterations of the airway microbiome is often associated with pulmonary diseases. For example, detection bacterial pathogen Moraxella catarrhalis in upper airways linked an increased risk to develop or exacerbate asthma. However, mechanisms by which M. cattarhalis augments allergic inflammation (AAI) remains unclear. We here characterized cellular and soluble mediators triggered excacerbation AAI wt IL-17 deficient as well animals treated TNF-alpha IL-6 neutralizing antibodies. compared type...
Similar to T-helper (Th) cells, CD8(+) T cells also differentiate into distinct subpopulations. However, the existence of IL-9-producing (Tc9) has not been elucidated so far. We show that murine activated in presence IL-4 plus TGF-β develop transient IL-9 producers characterized by specific IFN-γ and IL-10 expression patterns as well low cytotoxic function along with diminished CTL-associated transcription factors T-bet Eomesodermin. Similarly CD4(+) counterpart, Tc9 required for their...
Heat shock proteins (Hsps) play an important role in the development and pathogenicity of malaria parasites. One most prominent functions Hsps is to facilitate folding other proteins. are thought a crucial when parasites invade their host cells during subsequent hepatocytes red blood cells. It that maintain proteostasis under unfavourable conditions encounter environment. Although heat protein 70 (Hsp70) capable independent some proteins, its functional cooperation with 90 (Hsp90)...
The p14
Abstract Background IL‐17A and TNF synergistically promote inflammation tumorigenesis. Their interplay impact on ovarian carcinoma (OC) progression are, however, poorly understood. We addressed this question focusing mesothelial cells, whose interaction with tumor cells is known to play a pivotal role in transcoelomic metastasis formation. Methods Flow‐cytometry immunohistochemistry experiments were employed identify cellular sources of TNF. Changes transcriptomes secretomes determined by...
In Aurelia aurita, applied iodine induces medusa formation (strobilation). This process also occurs when the temperature is lowered. was found to increase oxidative stress resulting in an increased production of from iodide. One polyp produces several medusae (initially termed ephyrae) starting at polyp's oral end. The spreading strobilation down body column controlled by a feedback loop: ephyra anlagen decrease tyrosine content adjacent tissue producing melanin tyrosine. Endogenous able...
Apart from conventional CD4(+) Th17 cells, the cytokines IL-17A and IL-22 can also be produced by γδ T NK cells lymphoid tissue inducer (LTi) cells. develop precursor after T-cell receptor stimulation in presence of TGF-β, IL-6 IL-23. In contrast, a subset ("γδT17") is committed for fast IL-17 production already thymus; however, produce prolonged vitro via their plus Here, we show that T-, LTi- NKT differ extensively signalling requirements generation IL-22. While these totally depends on...
Abstract The T helper 9 (Th9) cell transcriptional network is formed by an equilibrium of signals induced cytokines and antigen presentation. Here we show that, within this network, two interferon regulatory factors (IRF), IRF1 IRF4, display opposing effects on Th9 differentiation. IRF4 dose-dependently promotes, whereas inhibits, IL-9 production. Likewise, inhibits production human cells. counteracts IRF4-driven Il9 promoter activity, have function activating histone modifications, thus...
ABSTRACT Effective CD8 + T cell responses play an important role in determining the course of a viral infection. Overwhelming antigen exposure can result suboptimal responses, leading to chronic This altered differentiation state, termed exhaustion, is characterized by reduced effector function, upregulation inhibitory receptors, and expression transcription factors. Prevention overwhelming limit exhaustion significant interest for control The factor interferon regulatory 9 (IRF9) component...
Regulatory T-cells induced via IL-2 and TGFβ in vitro (iTreg) suppress immune cells are potential therapeutics during autoimmunity. However, several reports described their re-differentiation into pathogenic vivo loss of key functional transcription factor (TF) FOXP3 after T-cell antigen receptor (TCR)-signalling vitro. Here, we show that TCR-activation antagonizes two necessary TFs for foxp3 gene transcription, which themselves regulated by phosphorylation. Although the tyrosine phosphatase...
Uraemic odour is a characteristic feature of patients with end-stage renal disease (ESRD). However, few investigations have been carried out into the composition exhaled air in ESRD undergoing haemodialysis (HD). Increases isoprene levels by factor up to 2.7 following HD reported.We attempted confirm these findings 50 using haemophan (n=23) or polysulphone (n=27) dialysis membranes. Parallel evaluation ambient air, calorie intake, medication and haemodynamic variables was performed. Samples...
In Brief Evidence on potential health hazards arising from exposure to volatile anesthetics remains controversial. Exposure may, in principle, be supervised by monitoring of ambient air or, alternatively, vivo. We used the Proton Transfer Reaction-Mass Spectrometry screen breath 40 operating room staff members before duty, 0, 1, 2, and 3 h after commencing duty consecutive day, control persons. Staff exhibited significantly increased sevoflurane levels exhaled with a mean 0.80 parts per...
The genus leishmania comprises different protozoan parasites which are causative agents of muco-cutaneous and systemic, potentially lethal diseases. After infection with the species Leishmania major, resistant mice expand Th1 cells stimulate macrophages for destruction. In contrast, susceptible generate Th2 deactivate macrophages, leading to systemic spread pathogens. Th-cell differentiation is determined within first days, cell requires IL-4, whereby initial IL-4 source often unknown. Mast...