A5024777470- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Inflammatory Bowel Disease
- IL-33, ST2, and ILC Pathways
- Receptor Mechanisms and Signaling
- Helicobacter pylori-related gastroenterology studies
- Microscopic Colitis
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- Asthma and respiratory diseases
- Mast cells and histamine
- CAR-T cell therapy research
- Toxoplasma gondii Research Studies
- Immune Response and Inflammation
- Acute Lymphoblastic Leukemia research
- Biosimilars and Bioanalytical Methods
- Platelet Disorders and Treatments
- Immune cells in cancer
- HIV/AIDS drug development and treatment
- Diabetes Treatment and Management
- Organic and Inorganic Chemical Reactions
- Neuropeptides and Animal Physiology
- Computational Drug Discovery Methods
- Adrenal Hormones and Disorders
- Blood disorders and treatments
Amgen (United States)
2010-2022
Electronic Sensor Technology (United States)
2016
Corixa Corporation
2004-2005
Infectious Disease Research Institute
2005
University of Washington
2005
Scripps Research Institute
2005
GlaxoSmithKline (Netherlands)
2004
Cellular Research (United States)
1996-2001
Palo Alto Research Center
1998
Palo Alto Institute
1997
Chronic intestinal inflammation, as seen in inflammatory bowel disease (IBD), results from an aberrant and poorly understood mucosal immune response to the microbiota of gastrointestinal tract genetically susceptible individuals. Here we used serological expression cloning identify commensal bacterial proteins that could contribute pathogenesis IBD. The dominant antigens identified were flagellins, molecules known activate innate immunity via Toll-like receptor 5 (TLR5), critical targets...
Chronic intestinal inflammation, as seen in inflammatory bowel disease (IBD), results from an aberrant and poorly understood mucosal immune response to the microbiota of gastrointestinal tract genetically susceptible individuals. Here we used serological expression cloning identify commensal bacterial proteins that could contribute pathogenesis IBD. The dominant antigens identified were flagellins, molecules known activate innate immunity via Toll-like receptor 5 (TLR5), critical targets...
Mice rendered deficient in the production of interleukin 10 (IL-10-/-) develop a chronic inflammatory bowel disease (IBD) that predominates colon and shares histopathological features with human IBD. Our aim was to identify which cell type(s) can mediate colitis IL-10-/- mice. We detected an influx immunoglobulin-positive cells into presence colon-reactive antibodies serum To assess pathogenic role for B cells, we generated cell-deficient (B-/-) strain B-/-IL-10-/- mice acquired severe...
Abstract The role for IL-10 in the immunopathogenesis of acute toxoplasmosis following peroral infection was examined both genetically susceptible C57BL/6 and resistant BALB/c mice. C57BL/6-background IL-10-targeted mutant (IL-10−/−) mice all died 2 wk after with 20 cysts ME49 strain, whereas only 20% control succumbed. Histological studies revealed necrosis small large intestines livers infected IL-10−/− intestine most severe pathologic response not observed Treatment either anti-CD4 or...
Abstract Current evidence indicates that the chronic inflammation observed in intestines of patients with inflammatory bowel disease is due to an aberrant immune response enteric flora. We have developed a lipid A-mimetic, CRX-526, which has antagonistic activity for TLR4 and can block interaction LPS system. CRX-526 prevent expression proinflammatory genes stimulated by vitro. This antagonist directly related its structure, particularly secondary fatty acyl chain length. In vivo, treatment...
Interleukin-10 (IL-10) is a cytokine which can inhibit T-cell and natural killer (NK) cell functions associated with cell-mediated immunity to intracellular infections. The production of IL-10 by mice infected Toxoplasma gondii has been implicated in the suppression lymphocyte proliferation observed during acute toxoplasmosis, as well susceptibility infection this parasite. We have used C57BL/6 lack functional gene (IL-10(-/-) mice) investigate role toxoplasmosis. Intraperitoneal IL-10(-/-)...
Previous studies have shown that the chronic inflammation observed in colon of IL-10-deficient (IL-10(-/-)) mice is mediated by CD4+ Th1 T cells and dependent on presence IFN-gamma for its initial development. As from IL-10(-/-) will cause colitis when transferred into recombinase-activating gene (Rag)-deficient recipients, we considered possibility recipients' NK could be an important source development colitis. Therefore, ability to Rag-deficient recipients had been depleted was tested....
Abstract IL-4 is associated with Th2-type immune responses and can either inhibit or, in some cases, promote Th1-type responses. We tested the effect of treatment on development inflammation CD4+CD45RBhigh T cell transfer model colitis, which has been characterized as a Th1-dependent disease. significantly accelerated colitis immunodeficient recipients (recombinase-activating gene-2 (Rag2)−/−) cells. Quantitative analysis mRNA expression colons IL-4-treated mice showed an up-regulation both...
IL-7 is a stromal cell-derived cytokine with well-established physiologic role in lymphocyte biology. This report describes an unexpected for the development of colitis T and B cell-deficient environment. Recombination-activating gene-2 (RAG-2)-deficient mice (RAG-2(-/-)) were exposed to subsequently maintained horizontally transmitted microbial flora that included Helicobacter hepaticus. These animals mounted strong myeloid cell response developed both systemic local signs severe colitis. A...
AMG X, a human neutralizing monoclonal antibody (mAb) against soluble protein, caused thrombocytopenia, platelet activation, reduced mean arterial pressure, and transient loss of consciousness in cynomolgus monkeys after first intravenous administration. In vitro, X induced activation platelets from macaque species but not humans or baboons. Other similar mAbs the same pharmacological target failed to induce these vivo vitro effects. addition, protein was known be expressed on platelets,...
Human peripheral blood mononuclear cells (PBMC) are routinely used in vitro to detect cytokine secretion as part of preclinical screens delineate agonistic and antagonistic action therapeutic monoclonal antibodies (mAbs). Preclinical value standard human PBMC assays release syndrome (CRS) has been questioned, they did not predict the "cytokine storm" that occurred when healthy volunteers were given a CD28-specific super-agonist mAb, TGN1412. In this article, we describe three-dimensional...
Mast cells play key roles in allergy, anaphylaxis/anaphylactoid reactions, and defense against pathogens/toxins. These contain cytoplasmic granules with a wide spectrum of pleotropic mediators that are released upon activation. While mast cell degranulation (MCD) occurs clustering the IgE receptor bound to antigen, MCD is also triggered through non-IgE-mediated mechanisms, one which via Mas-related G protein-coupled X2 (MRGPRX2). MRGPRX2 can be activated by many basic biogenic amines...
Cynomolgus monkeys dosed with a therapeutic monoclonal antibody (mAbY.1) at ≥50 mg/kg had unexpected acute thrombocytopenia (nadir ∼3,000 platelets/µl), sometimes decreases in red cell mass. Increased activated macrophages, mitotic figures, and erythrophagocytosis were observed the spleen. Binding of mAbY.1 to cynomolgus peripheral blood cells could not be detected vitro. induced phagocytosis platelets by monocytes from monkeys, but humans. mAbs sharing same constant domain (Fc) sequences,...
The propensity of HIV-1 to undergo sequence variation, particularly in the envelope glycoprotein gp120, complicates vaccine development and may enable virus evade ongoing immune responses infected individuals. We present here a molecular analysis effects this variability on human T cell recognition gp120. Synthetic peptides representing defined CD4+ epitope gp120 were used survey molecules from various strains for capacity be recognized context single MHC molecule, DR4. Variation affected at...
Immunomodulatory therapeutics such as monoclonal antibodies (mAb) carry an inherent risk of undesired immune reactions. One is cytokine release syndrome (CRS), a rapid systemic inflammatory response characterized by the secretion pro-inflammatory cytokines from cells. It crucial for patient safety to correctly identify potential CRS prior first-in-human dose administration. For this purpose, variety in vitro assays (CRA) are routinely used part preclinical assessment novel therapeutic mAbs....