A5067335835- Cytokine Signaling Pathways and Interactions
- interferon and immune responses
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Immune Response and Inflammation
- Viral Infections and Vectors
- RNA regulation and disease
- Mosquito-borne diseases and control
- Viral Infections and Immunology Research
- RNA Interference and Gene Delivery
- Atherosclerosis and Cardiovascular Diseases
- Cancer-related Molecular Pathways
- Malaria Research and Control
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Phosphodiesterase function and regulation
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Influenza Virus Research Studies
- IL-33, ST2, and ILC Pathways
- Immune cells in cancer
- Medicinal Plant Pharmacodynamics Research
- Complement system in diseases
- Pluripotent Stem Cells Research
- Adenosine and Purinergic Signaling
- Vascular Malformations and Hemangiomas
National Taiwan University
2015-2025
New York University
1997-2006
Kaplan (United States)
1997-2000
Montefiore Medical Center
1999
Albert Einstein College of Medicine
1999
Propagation of mouse embryonic stem (ES) cells in vitro requires exogenous leukemia inhibitory factor (LIF) or related cytokines. Potential downstream effectors the LIF signal ES include kinases Src, Jak, and mitogen-activated protein families transducer transcriptional activator STAT3. Activation nuclear STAT3 ability to grow as undifferentiated clones were monitored during withdrawal. A correlation was found between levels activity maintenance an phenotype at clonal density. In contrast,...
Abstract IFNs protect from virus infection by inducing an antiviral state and modulating the immune response. Using mice deficient in multiple aspects of IFN signaling, we found that type I II play distinct although complementing roles resolution influenza viral disease. Both types influenced profile cytokines produced T lymphocytes, with a significant bias toward Th2 differentiation occurring absence responsiveness to either IFN. However, Th1 through inhibition IFN-γ was not required...
Abstract NK cell functions were examined in mice with a targeted mutation of the STAT1 gene, an essential mediator IFN signaling. Mice deficient displayed impaired basal cytolytic activity vitro and unable to reject transplanted tumors vivo, despite presence normal numbers cells. IL-12 enhanced NK-mediated cytolysis, but poly(I:C) did not, similar phenotype occurred lacking IFNα receptors. Molecules involved activation lytic function cells (granzyme A, granzyme B, perforin, DAP10, DAP12)...
Abstract Type I IFNs are crucial cytokines of innate immunity for combating viral infections. Signaling through type IFN receptors triggers the activation STAT proteins, including STAT1, STAT2, and STAT3. Although an essential role STAT1 STAT2 IFN-induced antiviral response has been well established by studies gene-targeted mice human mutations, STAT3 this remains unclear. Using gain-of-function loss-of-function approaches, we demonstrated that negatively regulates IFN-mediated response....
Collectively our results strongly suggest that the alternative IFNα-mediated, STAT2/IRF9 dependent signaling pathway can induce a prolonged ISGF3-like transcriptome and generate an antiviral response analogous to ISGF3, independent of STAT1. Moreover, existence “STAT2/IRF9-specific” target genes predicts novel role STAT2 in IFNα signaling.
Abstract Lymphocytes derived from mice deficient in STAT1 showed reduced apoptosis and enhanced proliferation vitro. To understand the involvement of observed reduction apoptosis, we examined levels caspase bcl-2 family genes that are involved cell survival and/or apoptosis. The 1 11, two enzymes both cytokine protein processing induction were STAT1−/− cells compared with wild-type. However, comparable mice. also displayed an following TCR stimulation. This hyperproliferation could not be...
Type I interferon (IFN) is synthesized by most nucleated cells following viral infection. Robust IFN production in cell culture requires positive feedback expression of inducible signaling components, such as the transcription factor IRF7. However, role and IRF7 vivo may be more complex. We found that produced locally respiratory tract influenza virus-infected mice displayed characteristics feedback, including Stat1-dependent induction gene expression. was similarly stimulus-dependent...
Abstract Dengue virus (DENV) is the causative agent of dengue fever, hemorrhagic and shock syndrome endemic to tropical subtropical regions world. Our previous studies showed existence epitopes in C-terminal region DENV nonstructural protein 1 (NS1) which are cross-reactive with host Ags trigger anti–DENV NS1 Ab–mediated endothelial cell damage platelet dysfunction. To circumvent these potentially harmful events, we replaced corresponding from Japanese encephalitis create chimeric DJ...
Atherosclerosis is a chronic inflammatory disease of the blood vessels, characterized by atherosclerotic lesion formation. Vascular Smooth Muscle Cells (VSMC), macrophages (MΦ) and dendritic cells (DC) play crucial role in vascular inflammation atherosclerosis. Interferon (IFN)α, IFNγ Toll-like receptor (TLR)4 activate pro-inflammatory gene expression are pro-atherogenic. Gene regulation many genes has shown to rely on Signal Integration (SI) between IFNs TLR4 through combinatorial actions...
Daudi B lymphoblastoid cells are highly sensitive to the anti-growth and anti-viral effects of interferon (IFN). Unlike many cell lines, these show prolonged transcription IFN-stimulated genes following treatment with IFN-α. This response correlated continued presence activated factor, gene factor 3 (ISGF3). Pulse-chase labeling experiments indicated that half-life phosphorylation signal transducers activators (Stat)1 Stat2 was short (<2 h) although turnover proteins themselves slow (>24 h),...
During infections and inflammation, plasmacytoid dendritic cells (pDCs) are the most potent type I interferon (IFN-I)–producing cells. However, developmental origin of pDCs signals dictating pDC generation remain incompletely understood. Here, we report a synergistic role for IFN-I Flt3 ligand (FL) in development from common lymphoid progenitors (CLPs). Both conventional DCs (cDCs) were generated CLPs response to FL, whereas required higher concentrations FL concurrent signaling. An absence...
Elevated liver enzyme level is an outstanding feature in patients with dengue. However, the pathogenic mechanism of injury has not been clearly demonstrated. In this study, employing a mouse model we aimed to investigate immunopathogenic dengue injury. Immunocompetent C57BL/6 mice were infected intravenously virus strain 16681. Infected had transient viremia, detectable viral capsid gene and cleaved caspase 3 liver. mean time, NK cell T infiltrations peaked at days 1 5, respectively....
Highly pathogenic influenza viruses cause high levels of morbidity, including excessive infiltration leukocytes into the lungs, viral loads and a cytokine storm. However, details how these pathological features unfold in severe infections remain unclear. Accumulation Gr1 + CD11b myeloid cells has been observed highly but it is not clear why they accumulate severely inflamed lung. In this study, we selected cell population as target to investigate extreme inflammatory response during...
Abstract The CD47-SIRPα axis functions as an immune checkpoint, transmitting a “don’t eat me” signal to prevent macrophage-mediated phagocytosis of tumor cells. While CD47 is expressed on most cells and highly induced in cells, SIRPα phagocytes, including macrophages type II conventional dendritic (cDC2s). Blocking the binding between shown promote antitumor immunity. However, mechanism how CD47-Sirpα blockade regulates DC still unclear. Here we demonstrated that anti-CD47 and/or anti-Sirpα...
Major histocompatibility complex (MHC) class I antigens are constitutively expressed yet highly induced by interferon (IFN) during inflammation. We found that not only IFN-induced but also normal basal expression of MHC required IFN receptors and signal transducer activator transcription (STAT)1, providing genetic evidence for continuous signaling. Surprisingly, an IFN-independent requirement STAT1 was found, specifically in T lymphocytes, where fully accounted This pathway maintained...
Alpha/beta interferon (IFN-alpha/beta) triggers antiviral and antiproliferative responses in target cells through modulation of gene expression. The JAK-STAT pathway is the major mediator these biological effects activation transcription factors STAT1 STAT2, ablation studies have demonstrated that both STAT2 are required for most induced by IFN-alpha/beta. However, additional signaling pathways also activated IFN. Here, we show provoke a proliferative response T lymphocytes. While...
Like poliovirus infection, severe infection with enterovirus 71 (EV71) can cause neuropathology. Unlike poliovirus, EV71 is often associated hand-foot-and-mouth disease (HFMD). Here we established three mouse models for experimental the same clinical isolate of EV71. The NOD/SCID model unique development skin rash, an HFMD-like symptom. While mice developed limb paralysis and death at near-100% efficiency, gamma interferon receptor knockout (ifngr KO) stat-1 exhibited rates near 78% 30%,...
Marginal zone B (MZ B) cells can rapidly produce antibody in response to infection with blood-borne encapsulated pathogens. Although TLR-mediated activation of MZ is known trigger humoral immune response, the signal cascade directing this remains undefined. Here, we demonstrate that STAT1 plays an essential role cells. Further, TLR-induced IgM impaired a type I and II IFN-independent manner. activation, proliferation, apoptosis are not affected, both differentiation into plasma production...