Nora A. Barrett
A5074798857- Asthma and respiratory diseases
- IL-33, ST2, and ILC Pathways
- Allergic Rhinitis and Sensitization
- Eosinophilic Esophagitis
- Sinusitis and nasal conditions
- Mast cells and histamine
- Immune Cell Function and Interaction
- Drug-Induced Adverse Reactions
- Respiratory and Cough-Related Research
- Urticaria and Related Conditions
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Neonatal Respiratory Health Research
- Eosinophilic Disorders and Syndromes
- Antimicrobial Peptides and Activities
- Biochemical Analysis and Sensing Techniques
- Inflammatory mediators and NSAID effects
- Dermatology and Skin Diseases
- Tracheal and airway disorders
- Immunotherapy and Immune Responses
- Immune responses and vaccinations
- Olfactory and Sensory Function Studies
- Food Allergy and Anaphylaxis Research
- Pediatric health and respiratory diseases
- Extracellular vesicles in disease
- Neuroscience of respiration and sleep
Brigham and Women's Hospital
2016-2025
Harvard University
2016-2025
Women's Hospital
2021
Moscow Research and Clinical Center for Neuropsychiatry
2017
ENT and Allergy
2006
Ludwig-Maximilians-Universität München
1994
There is pressing urgency to understand the pathogenesis of severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2), which causes disease COVID-19. SARS-CoV-2 spike (S) protein binds angiotensin-converting enzyme (ACE2), and in concert with host proteases, principally transmembrane serine protease (TMPRSS2), promotes cellular entry. The cell subsets targeted by tissues factors that regulate ACE2 expression remain unknown. Here, we leverage human, non-human primate, mouse...
Abstract Neutrophils are implicated in multiple homeostatic and pathological processes, but whether functional diversity requires discrete neutrophil subsets is not known. Here, we apply single-cell RNA sequencing to neutrophils from normal inflamed mouse tissues. Whereas conventional clustering yields alternative organizational structures, diffusion mapping plus velocity discloses a single developmental spectrum, ordered chronologically. Termed here neutrotime, this spectrum extends...
Mast cells in type 2 airway inflammation exhibit heterogeneous inflammation-associated phenotypes and proliferate situ.
Abstract House dust mites are a significant source of airborne allergen worldwide, but there is little understanding how they so potently generate allergic inflammation. We found that extracts from the house Dermatophagoides farinae (Df) and pteronyssinus mold Aspergillus fumigatus stimulated rapid robust production cysteinyl leukotrienes (cys-LTs), proinflammatory lipid mediators, mouse bone marrow-derived dendritic cells (BMDCs). Con A affinity chromatography Df extract revealed relevant...
The innate signaling pathways for Th2 immunity activated by inhaled antigens are not well defined. We previously identified Dectin-2 as a receptor glycans in allergen extracts from the house dust mite Dermatophagoides farinae (Df) that mediates cysteinyl leukotriene (cys-LT) generation pulmonary CD11c+ cells and GM-CSF-cultured bone marrow (BMCs(GM-CSF)). Using lentiviral knockdown of BMCs(GM-CSF) adoptive transfer Df-pulsed to sensitize naive mice, we now report is critical development...
The leukotriene E 4 receptor, CysLT 3 R, regulates allergen-elicited expansion of airway brush cells and type 2 inflammation.
Group 2 innate lymphoid cells (ILC2s) and type helper T (Th2 cells) are the primary source of interleukin 5 (IL-5) IL-13 during (allergic) inflammation in lung. In Th2 cells, cell receptor (TCR) signaling activates transcription factors nuclear factor activated (NFAT), κB (NF-κB), activator protein 1 (AP-1) to induce cytokines. ILC2s lack a TCR respond instead locally produced cytokines such as IL-33. Although IL-33 induces AP-1 NF-κB, NFAT has not been described ILC2s. this study, we report...
Abstract Aspirin-exacerbated respiratory disease (AERD), a severe eosinophilic inflammatory disorder of the airways, involves overproduction cysteinyl leukotrienes (cysLTs), activation airway mast cells (MCs), and bronchoconstriction in response to nonselective cyclooxygenase inhibitors that deplete homeostatic PGE2. The mechanistic basis for MC this is unknown. We now demonstrate patients with AERD have markedly increased epithelial expression alarmin-like cytokine IL-33 nasal polyps, as...
Cysteinyl leukotrienes (cysLTs), leukotriene C4 (LTC4), LTD4, and LTE4 are proinflammatory lipid mediators with pathobiologic function in asthma. LTE4, the stable cysLT, is a weak agonist for type 1 2 cysLT receptors (CysLTRs), which constrict airway smooth muscle, but elicits airflow obstruction pulmonary inflammation patients We recently identified GPR99 as high-affinity receptor that mediates cutaneous vascular permeability. Here we demonstrate single intranasal exposure to extract from...
Aeroallergens and ATP elicit cysteinyl leukotrienes from nasal brush cells through the purinergic receptor P2Y2.
There is pressing urgency to better understand the pathogenesis of severe acute respiratory syndrome (SARS) coronavirus (CoV) clade SARS-CoV-2. SARS-CoV-2, like SARS-CoV, utilizes ACE2 bind host cells. While initial SARS-CoV-2 cell entry and infection depend on in concert with protease TMPRSS2 for spike (S) protein activation, specific subsets targeted by tissues, factors that regulate expression, remain unknown. Here, we leverage human non-human primate (NHP) single-cell RNA-sequencing...
Aeroallergen sensing by airway epithelial cells triggers pathogenic immune responses leading to type 2 inflammation, the hallmark of chronic diseases such as asthma. Tuft are rare and dominant source interleukin-25 (IL-25), an cytokine, cysteinyl leukotrienes (CysLTs), lipid mediators vascular permeability chemotaxis. How these two derived from same cell might cooperatively promote inflammation in airways has not been clarified. Here, we showed that inhalation parent leukotriene C4 (LTC4)...
The olfactory neuroepithelium serves as a sensory organ for odors and forms part of the nasal mucosal barrier. Olfactory neurons are surrounded supported by epithelial cells. Among them, microvillous cells (MVCs) strategically positioned at apical surface, but their specific functions enigmatic, relationship to other specialized is unclear. Here, we establish that family MVCs comprises tuft ionocytes in both mice humans. Integrating analysis respiratory epithelia, define distinct receptor...
Abstract Background Lung function is an independent predictor of mortality. We evaluated the lung trajectories a cohort patients with asthma receiving biologic therapy. Methods identified 229 monoclonal antibody‐naïve adult moderate‐to‐severe who initiated omalizumab, mepolizumab, or dupilumab between 2010 and 2022 in large healthcare system Boston, MA. Generalized additive mixed models were used to estimate during 156 weeks following initiation. Response was defined as improvement FEV 1...
Abstract The Th2 cell-dependent inflammatory response is a central component of asthma, and the ways in which it regulated critical question. cysteinyl leukotrienes (cys-LTs) are 5-lipoxygenase pathway products implicated particular, by their function as smooth muscle constrictors airways microvasculature. To elucidate additional roles for cys-LTs pathobiology pulmonary inflammation, we used an OVA sensitization challenge protocol with mice lacking leukotriene C4 synthase (LTC4S), terminal...