A5009233707- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Cytokine Signaling Pathways and Interactions
- Histone Deacetylase Inhibitors Research
- interferon and immune responses
- Immune Response and Inflammation
- Protein Degradation and Inhibitors
- Reproductive Physiology in Livestock
- Barrier Structure and Function Studies
- CRISPR and Genetic Engineering
- CAR-T cell therapy research
- Adipokines, Inflammation, and Metabolic Diseases
- Aortic aneurysm repair treatments
- Liver Diseases and Immunity
- RNA Research and Splicing
- Renal and Vascular Pathologies
- Adipose Tissue and Metabolism
- NF-κB Signaling Pathways
- Liver Disease Diagnosis and Treatment
- Immunodeficiency and Autoimmune Disorders
- PI3K/AKT/mTOR signaling in cancer
- Peripheral Artery Disease Management
- Macrophage Migration Inhibitory Factor
- Genomics, phytochemicals, and oxidative stress
Medical University of Vienna
2014-2024
Institute of Immunology
2022
Fukuoka University
2013-2019
Nara Medical University
2009-2018
Osaka University
2003-2014
The University of Tokyo
2002-2008
Kitasato University
2001-2006
Akita University
2003
Osaka Medical Center for Cancer and Cardiovascular Diseases
2003
Hamamatsu University School of Medicine
1987
A complex mechanism may be operational for dendritic cell (DC) maturation, wherein Toll-like receptor and other signaling pathways coordinated differently depending on the nature of pathogens, in order DC maturation to most effective a given threat. Here, we show that IFN-α/β is selectively required DCs induced by double-stranded RNA or viral infection vitro . Interestingly, still observed absence either two target genes IFN-α/β, TLR3 PKR (double-stranded-RNA-dependent protein kinase R),...
The recognition of microbial components by Toll-like receptors (TLRs) initiates signal transduction pathways, which trigger the expression a series target genes. It has been reported that TLR signaling is enhanced cytokines such as IFN-gamma, but mechanisms underlying this enhancement remain unclear. MyD88 adaptor, essential for many TLRs, recruits members IFN regulatory factor (IRF) family transcription factors, IRF5 and IRF7, to evoke activation In study we demonstrate IRF1, induced also...
A conundrum of innate antiviral immunity is how nucleic acid-sensing Toll-like receptors (TLRs) and RIG-I/MDA5 cooperate during virus infection. The conventional wisdom has been that the activation these receptor pathways evokes type I IFN (IFN) responses. Here, we provide evidence for a critical role 3 (TLR3)-dependent II signaling pathway in immune response against Coxsackievirus group B serotype (CVB3), member positive-stranded RNA family picornaviridae most prevalent associated with...
•NorUDCA reduces the number of hepatic innate and adaptive immune cells, including CD8+ T in Mdr2-/- model sclerosing cholangitis.•Independent its anticholestatic effects, NorUDCA exhibits direct immunomodulatory properties cells.•NorUDCA targets mTORC1 to modulate (phospho-) proteomic metabolic landscape cells.•Circulating cells from PSC patients show enhanced clonal expansion activity which are restricted by NorUDCA. Background & Aims24-Norursodeoxycholic acid (NorUDCA) is a novel...
Transcriptional pathways controlling the development of CD44 hi memory phenotype (MP) T cells with “innate-like” functions are not well understood. Here we show that BTB (bric-a-brac, tramtrack, broad complex) domain-containing protein promyelocytic leukemia zinc finger (PLZF) is expressed in , but lo CD4 + cells. Transgenic expression PLZF during cell and CD8 induced a intrinsic program leading to an increase peripheral MP corresponding decrease naïve The produced IFNγ upon PMA/ionomycin...
Abstract Background: Activation of both CD4 + T and CD8 cells is triggered by the engagement cell antigen receptor (TCR) with MHC/peptide complexes on antigen‐presenting cells. This process also requires other molecular interactions, which transmit co‐stimulatory signals to these To ensure an effective immune response, distinct subsets may additionally employ unique mechanism(s) for efficient activation. Results: We here show that mutant lacking IFN‐α/β signalling components are...
Cd8a and Cd8b1 coreceptor gene ( Cd8 ) expression is tightly controlled during T-cell development by the activity of five enhancers E8 I –E8 V ). Here we demonstrate a unique transcriptional program regulating CD8 + effector differentiation. The enhancer Runx/core-binding factor-β (CBFβ) complexes were required for establishment this regulatory circuit, because -, Runx3-, or CBFβ-deficient T cells down-regulated CD8α activation. This finding correlated with enhanced repressive histone marks...
Insults to cellular health cause p53 protein accumulation, and loss of function leads tumorigenesis. Thus, has be tightly controlled. Here we report that the BTB/POZ domain transcription factor PATZ1 (MAZR), previously known for its transcriptional suppressor functions in T lymphocytes, is a crucial regulator p53. The novel role as an inhibitor marks gene proto-oncogene. PATZ1-deficient cells have reduced proliferative capacity, which assessed by transcriptome sequencing (RNA-Seq) real-time...
Some effector CD4+ T cell subsets display cytotoxic activity, thus breaking the functional dichotomy of helper and CD8+ lymphocytes. However, molecular mechanisms regulating lymphocyte (CD4+ CTL) differentiation are poorly understood. Here we show that levels histone deacetylases 1 2 (HDAC1-HDAC2) key determinants CTL differentiation. Deletions both Hdac1 Hdac2 alleles (HDAC1cKO-HDAC2HET) in cells induced a program was controlled by IFN-γ-JAK1/2-STAT1 signaling. In vitro, activated...
Th-inducing Pox virus and zinc finger/Krüppel-like factor (ThPOK) is a key commitment for CD4(+) lineage T cells essential the maintenance of CD4 integrity; thus, expression ThPOK has to be tightly controlled. In this article, we demonstrate that Myc-associated finger-related (MAZR) Runt-related transcription 1 (Runx1) together repressed in preselection double-positive thymocytes, whereas MAZR acted synergy with Runx3 repression CD8(+) cells. Furthermore, MAZR-Runx1 MAZR-Runx3 double-mutant...
How functionally diverse populations of pathogen-specific killer T cells are generated during an immune response remains unclear. Here, we propose that fine-tuning CD8αβ co-receptor levels via histone acetylation plays a role in lineage fate. We show lysine acetyltransferase 6A (KAT6A) is responsible for maintaining permissive Cd8 gene transcription and enabling robust effector responses infection. KAT6A-deficient CD8+ downregulated surface CD8 expression clonal expansion, finding linked to...
Abstract Oncostatin M (OSM) is a member of the interleukin (IL)‐6 family cytokines. We previously demonstrated that OSM induces blood‐brain barrier (BBB) impairment. However, functional characterization IL‐6 cytokines in BBB regulation and cytokine‐related intracellular signaling pathway remain unclear. In this study, we demonstrate among cytokines, including leukemia inhibitory factor (LIF), most potent molecule for inducing dysfunction via prolonged activation signal transducer activator...
Nuclear receptor corepressor 1 (NCOR1) is a transcriptional regulator bridging repressive chromatin modifying enzymes with transcription factors. NCOR1 regulates many biological processes, however its role in T cells not known. Here we show that Cd4-Cre-mediated deletion of (NCOR1 cKO
Proper development of the immune system is an intricate process dependent on many factors, including intact DNA damage response. The double-strand break signaling kinase ATM and its cofactor NBS1 are required during T cell for maintenance genomic stability. role a second cofactor, ATMIN (also known as ASCIZ) in cells much less clear, whether function synergy unknown. Here, we investigate roles NBS1, either alone or combination, using murine models. We show loss led to developmental block at...
Mast cells are key players in type I hypersensitivity reactions humans and mice their activity has to be tightly controlled. Previous studies implicated the transcription factor MAZR regulation of mast cell function. To study role cells, we generated a conditional Mazr allele crossed MazrF/F with Vav-iCre deleter strain, which is active all hematopoietic cells. MAZR-null BM-derived (BMMC) were phenotypically indistinguishable from wild-type BMMCs, although numbers IL-3 MazrF/FVav-iCre BMMCs...
Abstract CD8 coreceptor expression is dynamically regulated during thymocyte development and tightly controlled by the activity of at least 5 different cis-regulatory elements. Despite detailed characterization Cd8 loci, regulation complex pattern cannot be fully explained known enhancers. In this study, we revisited Cd8ab gene with bioinformatics transgenic reporter approaches to search for additional This led identification an ECR (ECR-4), which in assays, directed preferentially...