A5018281721- IL-33, ST2, and ILC Pathways
- Asthma and respiratory diseases
- Eosinophilic Esophagitis
- Legionella and Acanthamoeba research
- Allergic Rhinitis and Sensitization
- Mast cells and histamine
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Vibrio bacteria research studies
- Bacterial biofilms and quorum sensing
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Food Allergy and Anaphylaxis Research
- Inflammasome and immune disorders
- Dermatology and Skin Diseases
- Urticaria and Related Conditions
- Neuroinflammation and Neurodegeneration Mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Inhalation and Respiratory Drug Delivery
- Biochemical Analysis and Sensing Techniques
- Immune Response and Inflammation
- Olfactory and Sensory Function Studies
- Autophagy in Disease and Therapy
- Viral Infections and Immunology Research
- Pediatric health and respiratory diseases
- Adipokines, Inflammation, and Metabolic Diseases
Regeneron (United States)
2019-2025
Tufts University
2014-2022
Howard Hughes Medical Institute
2014-2015
Jackson Laboratory
2011
Abstract Background Dupilumab, a fully human monoclonal antibody that binds IL‐4Rα and inhibits signaling of both IL‐4 IL‐13, has shown efficacy across multiple diseases with underlying type 2 signatures is approved for treatment asthma, atopic dermatitis, chronic sinusitis nasal polyposis. We sought to provide comprehensive analysis the redundant distinct roles IL‐13 in inflammation report dupilumab mechanisms action. Methods Using primary cell assays mouse model house dust mite–induced we...
Immunoglobulin E (IgE) plays an important role in allergic diseases. Nevertheless, the source of IgE serological memory remains controversial. We reexamined mechanism allergy using a dual reporter system to track IgE+ plasma cells mice. Short-term allergen exposure resulted generation that resided mainly secondary lymphoid organs and produced was unable degranulate mast cells. In contrast, chronic led long-lived were primarily derived from sequential class switching IgG1, accumulated bone...
Type 2 (T2) asthma is characterized by airflow limitations and elevated levels of blood sputum eosinophils, fractional exhaled nitric oxide, IgE, periostin. While eosinophils are associated with exacerbations, the contribution to lung inflammation, remodeling function remains largely hypothetical. To determine effect T2 cytokines IL-4, IL-13 IL-5 on eosinophil biology compare impact depleting just versus inhibiting all aspects inflammation airway inflammation. Human or endothelial cells...
Many pathogens, particularly those that require their host for survival, have devised mechanisms to subvert the immune response in order survive and replicate intracellularly. Legionella pneumophila, causative agent of Legionnaires' disease, promotes intracellular growth by translocating proteins into its cytosol through type IV protein secretion machinery. At least 5 bacterial translocated effectors interfere with function cell elongation factors, blocking translation causing induction a...
Following activation by cognate antigen, B cells undergo fine-tuning of their antigen receptors and may ultimately differentiate into antibody-secreting (ASCs). While antigen-specific that express surface (B cell [BCRs]) can be readily cloned sequenced following flow sorting, ASCs lack BCRs cannot easily profiled. Here, we report an approach, TRAPnSeq (antigen specificity mapping through immunoglobulin [Ig] secretion TRAP Sequencing), allows capture secreted antibodies on the ASCs, which in...
Immunoglobulin E (IgE) is a key driver of type 1 hypersensitivity reactions and allergic disorders, which are globally increasing in number severity. Although eliminating pathogenic IgE may be powerful way to treat allergy, no therapeutic strategy reported date can fully ablate production. Interleukin-4 receptor α (IL-4Rα) signaling required for class switching, IL-4Rα blockade gradually reduces, but does not eliminate, IgE. The persistence after due long-lived + plasma cells that maintain...
Understanding the phenotypic and transcriptional signature of immunoglobulin E (IgE)–producing cells is fundamental to plasma cell (PC) biology development therapeutic interventions for allergy. Here, using a mouse model intranasal house dust mite (HDM) exposure, we showed that short-lived IgE PCs emerge in lung draining lymph nodes (dLNs) during early exposure (<3 weeks) long-lived accumulate bone marrow (BM) with prolonged (>7 weeks). had distinct surface gene expression profiles...
IL-4 and IL-13 have non-redundant effects in olfaction, with loss of smell mice evoked only by intranasal administration IL-4, but not IL-13. IL-4-evoked pathophysiological on olfaction is independent compromised structural integrity the olfactory neuroepithelium. IL-4-IL-4Rα signaling modulates neuronal crosstalk immune cells, suggesting a functional link between impairment neuroinflammation. Abbreviations: IL, interleukin; KO, knock-out; wk, week; WT, wild-type.
Legionella pneumophila grows within membrane-bound vacuoles in alveolar macrophages during human disease. Pathogen manipulation of the host cell is driven by bacterial proteins translocated through a type IV secretion system (T4SS). Although protein synthesis infection arrested action several these effectors, translation subset predicted to restrict pathogen maintained. To identify spectrum selectively synthesized after L. challenge, infected with were allowed incorporate amino acid analog...
Nominally resistant mouse strains such as C57BL/6 (B6) harbor latent type 1 diabetes susceptibility genes uncovered in outcross to disease-susceptible NOD mice. However, identification of possible recessively acting B6-derived is limited because very few F2 progeny derived from outcrossing this strain with develop spontaneous autoimmune diabetes. Thus, we assessed whether a transgenic T-cell receptor (TCR) disease transfer model allowed the mapping B6 genetic loci that proper context...
Increased use of antiviral monoclonal antibodies (mAbs) for treatment and prophylaxis necessitates better understanding their impact on endogenous immunity to vaccines viruses. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic presented an opportunity study in individuals who received mAbs were subsequently immunized with encoding the mAb-targeted viral spike antigen. Here, we describe administration antibody combination, casirivimab plus imdevimab (CAS+IMD), immune...