A5077318322- IL-33, ST2, and ILC Pathways
- Immune Cell Function and Interaction
- Eosinophilic Esophagitis
- Helicobacter pylori-related gastroenterology studies
- Pediatric health and respiratory diseases
- Parasites and Host Interactions
- Immunotherapy and Immune Responses
- Neonatal Respiratory Health Research
- Asthma and respiratory diseases
- Fungal Infections and Studies
- NF-κB Signaling Pathways
- Galectins and Cancer Biology
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Antimicrobial Peptides and Activities
- Cancer Cells and Metastasis
- Immune Response and Inflammation
- Psoriasis: Treatment and Pathogenesis
- Antifungal resistance and susceptibility
- Cytokine Signaling Pathways and Interactions
- Cancer-related gene regulation
- T-cell and B-cell Immunology
- Streptococcal Infections and Treatments
- Reproductive System and Pregnancy
- Allergic Rhinitis and Sensitization
- Peptidase Inhibition and Analysis
University of Pennsylvania
2018-2025
California University of Pennsylvania
2019-2025
University of California, San Francisco
2012-2021
Philadelphia VA Medical Center
2018
University of California, Davis
2007-2015
National Taiwan University
2008-2010
Abstract Mucin over-production is one of the hallmarks chronic airway diseases such as obstructive pulmonary disease, asthma, and cystic fibrosis. NF-κB activation in epithelial cells has been shown to play a positive inflammatory role diseases; however, mucin gene expression unresolved. In this study, we have that proinflammatory cytokines, IL-1β IL-17A, both which utilize pathway, are potent inducers (MUC)5AC mRNA protein synthesis by well-differentiated primary normal human bronchial cell...
Parasitic helminths are a major cause of chronic human disease, affecting more than 3 billion people worldwide. Host protection against most parasitic relies upon Type 2 cytokine production, but the mechanisms that regulate interleukin (IL) 4 and 13 production from CD4 + T helper cells (T H 2) innate lymphoid type (ILC2s) remain incompletely understood. The epithelial cell-derived cytokines IL-25 IL-33 promote responses, extent functional redundancy between these is unclear whether memory...
The pore-forming protein perforin-2 facilitates IL-33 release from dendritic cells.
A major pathological feature of chronic airway diseases is the elevated expression gel-forming mucins. NF-κB activation in epithelial cells has been shown to play a proinflammatory role diseases; however, specific mucin gene not characterized. In this study, we show that cytokines, IL-1β and IL-17A, both which use pathway, are potent inducers MUC5B mRNA well differentiated primary normal human bronchial cell line, HBE1. induction by these cytokines was time- dose-dependent, attenuated small...
Intestinal epithelial cells (IEC) have important functions in nutrient absorption, barrier integrity, regeneration, pathogen-sensing, and mucus secretion. Goblet are a specialized cell type of IEC that secrete Trefoil factor 3 (TFF3) to regulate viscosity wound healing, but whether TFF3-responsiveness requires receptor is unclear. Here, we show leucine rich repeat nogo-interacting protein 2 (LINGO2) essential for TFF3-mediated functions. LINGO2 immunoprecipitates with TFF3, co-localizes TFF3...
Coordinated efforts between macrophages and epithelia are considered essential for wound healing, but the macrophage-derived molecules responsible repair poorly defined. This work demonstrates that lung rely upon Trefoil factor 2 to promote epithelial proliferation following damage caused by sterile wounding, Nippostrongylus brasiliensis or Bleomycin sulfate. Unexpectedly, presence of T, B, ILC populations was not macrophage-driven repair. Instead, conditional deletion TFF2 in...
Abstract CR3 on primary macrophage participates in phagocytosis of Histoplasma yeast and collaborates with dectin-1 cytokine response to the fungus. The cells dimorphic fungal pathogen reside primarily within macrophages an infected host; interaction between has a profound impact host defense against We used blocking antibodies saccharides identify receptors that participate Histoplasma. results show sialic acids were involved CR3, although not only receptor involved, was responsible for...
Statins are widely used to prevent cardiovascular disease. In addition their inhibitory effects on cholesterol synthesis, statins have beneficial in patients with sepsis and pneumonia, although molecular mechanisms mostly remained unclear. Using human airway epithelial cells as a proper vitro model, we show that prior exposure physiological nanomolar serum concentrations of simvastatin (ranging from 10-1,000 nM) confers significant cellular resistance the cytotoxicity pneumolysin,...
Abstract Immunity against skin-invasive pathogens requires mechanisms that rapidly detect, repel or immobilize the infectious agent. While bacteria often cause painful cutaneous reactions, host skin invasion by human parasitic helminth Schistosoma mansoni goes unnoticed. This study investigated role of pain-sensing afferents express ion channel Transient Receptor Potential Vanilloid 1 (TRPV1) in detection and initiation immunity S. . Data show mice infected with have reduced behavioral...
Interleukin 33 (IL-33) is a pleiotropic cytokine released from diverse cell types that regulate both pro- and anti-inflammatory responses during pathogen infection. However, it remains unclear whether IL-33 controls key aspects of cutaneous immunity against skin-penetrating parasites. In this study, mice percutaneously infected with the parasitic helminth Strongyloides ratti were investigated to understand mechanisms anamnestic at skin barrier. Surprisingly, lacking Type 2 transcription...
Airway epithelial cells are the first line of defense against viral infections and instrumental in coordinating inflammatory response. In this study, we demonstrate synergistic stimulation CXCL10 mRNA protein, a key chemokine responsible for early immune response to infection, following treatment airway with IFN γ influenza virus. The synergism also occurred when were treated replication mimicker (dsRNA) both vitro vivo. Despite requirement type I interferon (IFNAR) signaling dsRNA-induced...
How the metabolic demand of parasitism affects immune-mediated resistance is poorly understood. Immunity against parasitic helminths requires M2 cells and IL-13, secreted by CD4(+) Th2 group 2 innate lymphoid (ILC2), but whether certain enzymes control disease outcome has not been addressed. This study demonstrates that AMP-activated protein kinase (AMPK), a key driver cellular energy, regulates type immunity restricts lung injury following hookworm infection. Mice with selective deficiency...
Antigen encounter directs CD4+ T cells to differentiate into helper or regulatory cells. This process focuses the immune response on invading pathogen and limits tissue damage. Mechanisms that govern cell versus fate remain poorly understood. Here, we show E3 ubiquitin ligase Cul5 determines selection in by regulating IL-4 receptor signaling. Mice lacking develop Th2 Th9 inflammation pathophysiological features of atopic asthma. Following activation, forms a complex with CIS pJak1. deletion...
The impact of the host immune environment on parasite transcription and fitness is currently unknown. It widely held that hookworm infections have an immunomodulatory host, but whether converse true remains unclear. Immunity against adult-stage hookworms largely mediated by Type 2 responses driven factor Signal Transducer Activator Transcription 6 (STAT6). This study investigated serial passage rodent Nippostrongylus brasiliensis in STAT6-deficient mice (STAT6 KO) caused changes parasites...
Host defense at the mucosal interface requires collaborative interactions between diverse cell lineages. Epithelial cells damaged by microbial invaders release reparative proteins such as Trefoil factor family (TFF) peptides that functionally restore barrier integrity. However, whether TFF and their receptors also serve instructive roles for immune function during infection is incompletely understood. Here, we demonstrate intestinal trefoil factor, TFF3, restrains (T helper) T
Helminths are distinct from microbial pathogens in both size and complexity, the likely evolutionary driving force for type 2 immunity. CD4+ helper T cells can coordinate worm clearance prevent immunopathology, but issues of cell antigen specificity context helminth-induced Th2 regulatory (Treg) responses have not been addressed. Herein, we generated a novel transgenic line gastrointestinal nematode Strongyloides ratti expressing immunodominant epitope 2W1S as fusion protein with green...
Aim: Recovery of damaged mucosal surfaces following inflammatory insult requires diverse regenerative mechanisms that remain poorly defined. Previously, we demonstrated the reparative actions Trefoil Factor 3 (TFF3) depend upon enigmatic receptor, leucine rich repeat and immunoglobulin-like domain containing nogo receptor 2 (LINGO2). This study examined related orphan LINGO3 in context intestinal tissue damage to determine whether LINGO family members are generally important for wound...
IL-33 is an IL-1 family cytokine that signals through its cognate receptor, ST2, to regulate inflammation. Whether serves a pathogenic or protective role during inflammatory bowel disease controversial. Herein, two different strains of cell-specific conditionally deficient mice were used compare the myeloid- versus intestinal epithelial cell-derived dextran sodium sulfate-induced colitis. Data show loss CD11c-restricted exacerbated tissue pathology, coinciding with increased Il6 levels and...
Whether conventional dendritic cells (cDC) acquire subset identity under direction of Wnt family glycoproteins is unknown. We demonstrate that Wnt4, a β-catenin-independent ligand, produced by both hematopoietic and nonhematopoietic necessary sufficient for preconventional DC1/cDC1 maintenance. Whereas bone marrow cDC precursors undergo phosphoJNK/c-Jun activation upon Wnt4 treatment, loss in CD11cCreWnt4flox/flox mice impaired differentiation CD24+, Clec9A+, CD103+ cDC1 compared with...
ABSTRACT Myeloid phagocytes are essential for antifungal immunity against pulmonary Aspergillus fumigatus and systemic Candida albicans infections. However, the molecular mechanisms underlying fungal clearance by remain incompletely understood. In this study, we investigated role of perforin-2 ( Mpeg1 ) in immunity. We found that -/- mice generated on a mixed C57BL/6J-DBA/2 background exhibited enhanced survival, reduced lung burden, greater neutrophil killing activity compared to wild-type...