A5061309096- Asthma and respiratory diseases
- IL-33, ST2, and ILC Pathways
- Eosinophilic Esophagitis
- Allergic Rhinitis and Sensitization
- Immune Cell Function and Interaction
- Mast cells and histamine
- Respiratory viral infections research
- Food Allergy and Anaphylaxis Research
- Neonatal Respiratory Health Research
- Pediatric health and respiratory diseases
- Immune Response and Inflammation
- Studies on Chitinases and Chitosanases
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Respiratory and Cough-Related Research
- Immunotherapy and Immune Responses
- Complement system in diseases
- Advanced Glycation End Products research
- Chemokine receptors and signaling
- Parasitic Diseases Research and Treatment
- Invertebrate Immune Response Mechanisms
- Influenza Virus Research Studies
- T-cell and B-cell Immunology
- Inhalation and Respiratory Drug Delivery
- Whipple's Disease and Interleukins
- Immune cells in cancer
AstraZeneca (United Kingdom)
2020-2023
Roche (Switzerland)
2023
AstraZeneca (Sweden)
2022
AstraZeneca (United States)
2020-2021
AstraZeneca (Switzerland)
2019
Hacettepe University
2011
Autoimmune Technologies (United States)
2011
Harvard University Press
2002-2009
Harvard University
1999-2007
Boston Children's Hospital
1999-2007
Features of chronic asthma include airway hyperresponsiveness, inflammatory infiltrates, and structural changes in the airways, termed remodeling. The contribution eosinophils, cells associated with allergy, remains to be established. We show that mice a total ablation eosinophil lineage, increases hyperresponsiveness mucus secretion were similar those observed wild-type mice, but eosinophil-deficient significantly protected from peribronchiolar collagen deposition smooth muscle. These data...
To study the biologic role of migration inhibitory factor (MIF), a pleiotropic cytokine, we generated mouse strain lacking MIF by gene targeting in embryonic stem cells. Analysis during sepsis showed that MIF−/− mice were resistant to lethal effects high dose bacterial lipopolysaccharide (LPS), or Staphylococcus aureus enterotoxin B (SEB) with d-galactosamine and had lower plasma levels tumor necrosis α (TNF-α) than did wild-type mice, but normal interleukin (IL)-6 IL-10. When stimulated LPS...
Mouse breast regression protein 39 (BRP-39; Chi3l1) and its human homologue YKL-40 are chitinase-like proteins that lack chitinase activity. Although is expressed in exaggerated quantities correlates with disease activity asthma many other disorders, the biological properties of BRP-39/YKL-40 have only been rudimentarily defined. We describe generation characterization BRP-39−/− mice, transgenic mice BRP-39 produce their pulmonary epithelium. Studies these demonstrated animals markedly...
CCR3 is a chemokine receptor initially thought specific to eosinophils but subsequently identified on TH2 cell subsets, basophils, mast cells, neural tissue, and some epithelia. Because of the prominent role these cells in allergic disease, including asthma, we generated mice deficient determine its contribution model airway disease. Here show that important for basal trafficking intestinal mucosa not lung. In contrast, disruption significantly curtails eosinophil recruitment lung after...
Because eosinophils recruited into the airways in allergic diseases are exposed to inhaled allergens, we evaluated whether within endobronchial lumen can function vivo as antigen-presenting cells for antigens. We recovered from after aerosol antigen challenge sensitized mice or peritoneal cavities of IL-5 transgenic and fluorescently labeled these ex vivo. These cells, instilled intratracheally normal mice, migrated draining paratracheal lymph nodes localized T cell–rich paracortical areas....
C5a anaphylatoxin, a potent inflammatory mediator, is known to act through specific G protein coupled receptor. However, some of the complex effects in vivo may not be explained solely by deletion Here, we show that an orphan receptor, identified as C5L2, high affinity binding protein. Unlike previously described C5aR, C5L2 obligately uncoupled from heterotrimeric proteins, part virtue amino acid alteration so-called DRY sequence at end third transmembrane segement. Both human and murine...
Challenge of the airways sensitized guinea pigs with aerosolized ovalbumin resulted in an early phase microvascular protein leakage and a delayed eosinophil accumulation airway lumen, as measured using bronchoalveolar lavage (BAL). Immunoreactive eotaxin levels rose tissue BAL fluid to peak at 6 h falling low by 12 h. Eosinophil numbers correlated until but eosinophils persisted last measurement time point 24 In contrast, few appeared over first h, major trafficking through epithelium...
The CC chemokine receptor 3 (CCR3) is expressed by eosinophils, mast cells, and Th2 cells. We used CCR3–/– mice to assess the role of CCR3 in a murine model allergic skin inflammation induced repeated epicutaneous sensitization with ovalbumin (OVA), characterized eosinophil infiltration, local expression cytokines, airway hyperresponsiveness (AHR) inhaled antigen. Eosinophils product major basic protein were absent from sham OVA-sensitized mice. Mast cell numbers IL-4 mRNA normal mice,...
The CC chemokine receptor 3 (CCR3) is expressed by eosinophils, mast cells, and Th2 cells. We used CCR3–/– mice to assess the role of CCR3 in a murine model allergic skin inflammation induced repeated epicutaneous sensitization with ovalbumin (OVA), characterized eosinophil infiltration, local expression cytokines, airway hyperresponsiveness (AHR) inhaled antigen. Eosinophils product major basic protein were absent from sham OVA-sensitized mice. Mast cell numbers IL-4 mRNA normal mice,...
IL-9 is a pleiotropic cytokine that has multiple effects on structural as well numerous hematopoietic cells, which are central to the pathogenesis of asthma.
Recognition of DNA and RNA molecules derived from pathogens or self-antigen is one way the mammalian immune system senses infection tissue damage. Activation signaling receptors by nucleic acids controlled limiting access to intracellular receptors, but mechanisms which endosome-resident encounter extracellular space are largely undefined. In this study, we show that receptor for advanced glycation end-products (RAGE) promoted uptake into endosomes lowered recognition threshold activation...
Eosinophils have been implicated as playing a major role in allergic airway responses. However, the importance of these cells to development this disease has remained ambiguous despite many studies, partly because lack appropriate model systems. In study, using transgenic murine models, we more clearly delineate for eosinophils asthma. We report that, contrast results obtained on BALB/c background, eosinophil-deficient C57BL/6 ΔdblGATA mice (eosinophil-null via ΔDblGATA1 mutation) reduced...
Cigarette smoking is the main risk factor for development of chronic obstructive pulmonary disease (COPD), a major cause morbidity and mortality worldwide. Despite this, cellular molecular mechanisms that contribute to COPD pathogenesis are still poorly understood.The objective this study was assess IL-1 α β expression in patients investigate their respective roles perpetuating cigarette smoke-induced inflammation. Functional studies were pursued smoke-exposed mice using gene-deficient...
Eosinophils natively inhabit the small intestine, but a functional role for them there has remained elusive. Here, we show that eosinophil-deficient mice were protected from induction of Th2-mediated peanut food allergy and anaphylaxis, Th2 priming was restored by reconstitution with il4+/+ or il4−/− eosinophils. controlled CD103+ dendritic cell (DC) activation migration intestine to draining lymph nodes, events necessary priming. Eosinophil in vitro vivo led degranulation eosinophil...
Release of endogenous damage associated molecular patterns (DAMPs), including members the S100 family, are with infection, cellular stress, tissue and cancer. The extracellular functions this family calcium binding proteins, particularly S100A8, S100A9 S100A12, being delineated. They appear to mediate their via receptor for advanced glycation endproducts (RAGE) or TLR4, but there remains considerable uncertainty over relative physiological roles these DAMPs pattern recognition receptors. In...
Background Epithelial damage, repair and remodelling are critical features of chronic airway diseases including obstructive pulmonary disease (COPD). Interleukin (IL)-33 released from damaged epithelia causes inflammation via its receptor, serum stimulation-2 (ST2). Oxidation IL-33 to a non-ST2-binding form (IL-33 ox ) is thought limit activity. We investigated whether has functional activities that independent ST2 in the epithelium. Methods In vitro epithelial damage assays...