David B. Jacoby
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View article: Eosinophil peroxidase induces inflammation in a mouse model of dermatitis
Eosinophil peroxidase induces inflammation in a mouse model of dermatitis Open
Eosinophils play an important role in mediating itch and inflammation in dermatitis. The role of the eosinophil granule protein eosinophil peroxidase (EPX) in mediating inflammation and itch was tested in a dermatitis mouse model. Mice wer…
View article: Maternal high-fat diet programs offspring airway hyperinnervation and hyperresponsiveness
Maternal high-fat diet programs offspring airway hyperinnervation and hyperresponsiveness Open
The impact of diet-induced maternal obesity on offspring airway hyperresponsiveness was studied in a diversity outbred mouse model that mirrors human genetic diversity. Female mice were started on high-fat or regular diet 8 weeks before br…
View article: Parasympathetic Airway Hyperreactivity Is Enhanced in Acute but Not Chronic Eosinophilic Asthma Mouse Models
Parasympathetic Airway Hyperreactivity Is Enhanced in Acute but Not Chronic Eosinophilic Asthma Mouse Models Open
Airway hyperreactivity in asthma is mediated by airway nerves, including sensory nerves in airway epithelium and parasympathetic nerves innervating airway smooth muscle. Isolating the function of these two nerve populations in vivo, to dis…
View article: Eosinophils prevent diet-induced airway hyperresponsiveness in mice on a high-fat diet
Eosinophils prevent diet-induced airway hyperresponsiveness in mice on a high-fat diet Open
This study investigates how eosinophils influence systemic metabolism and airway function in obesity. Known for their immune functions, eosinophils also mitigate obesity-related hyperinsulinemia, reducing airway hyperresponsiveness in obes…
View article: Grandmaternal allergen sensitization reprograms epigenetic and airway responses to allergen in second-generation offspring
Grandmaternal allergen sensitization reprograms epigenetic and airway responses to allergen in second-generation offspring Open
Asthma susceptibility is influenced by environmental, genetic, and epigenetic factors. This study shows that maternal allergen exposure during pregnancy promotes unique epigenetic trajectories in second-generation offspring at baseline and…
View article: Grandmaternal allergen sensitization reprograms epigenetic and airway responses to allergen in second generation offspring
Grandmaternal allergen sensitization reprograms epigenetic and airway responses to allergen in second generation offspring Open
SUPPLEMENTARY FIGURE LEGEND Supplemental Figure 1. Grandmaternal allergen exposure regulates differentially methylated cytosines in airway epithelium of second-generation offspring at baseline and after allergen sensitization. Grandmaterna…
View article: Grandmaternal allergen sensitization reprograms epigenetic and airway responses to allergen in second generation offspring
Grandmaternal allergen sensitization reprograms epigenetic and airway responses to allergen in second generation offspring Open
SUPPLEMENTARY FIGURE LEGEND Supplemental Figure 1. Grandmaternal allergen sensitization during pregnancy regulates differentially methylated cytosines in airway epithelium of second-generation offspring at baseline and after allergen sensi…
View article: Grandmaternal allergen sensitization reprograms epigenetic and airway responses to allergen in second generation offspring
Grandmaternal allergen sensitization reprograms epigenetic and airway responses to allergen in second generation offspring Open
SUPPLEMENTARY FIGURE LEGEND Supplemental Figure 1. Grandmaternal allergen sensitization during pregnancy regulates differentially methylated cytosines in airway epithelium of second-generation offspring at baseline and after allergen sensi…
View article: Maternal high-fat diet increases airway sensory innervation and reflex bronchoconstriction in adult offspring
Maternal high-fat diet increases airway sensory innervation and reflex bronchoconstriction in adult offspring Open
Our study reveals a novel potential mechanism, by which maternal high-fat diet increases the risk and severity of asthma in offspring. We found that exposure to maternal high-fat diet in mice leads to hyperinnervation of airway sensory ner…
View article: Insulin increases sensory nerve density and reflex bronchoconstriction in obese mice
Insulin increases sensory nerve density and reflex bronchoconstriction in obese mice Open
Obesity-induced asthma responds poorly to all current pharmacological interventions, including steroids, suggesting that classic, eosinophilic inflammation is not a mechanism. Since insulin resistance and hyperinsulinemia are common in obe…
View article: Grandmaternal allergen exposure causes distinct epigenetic trajectories in offspring associated with airway hyperreactivity and inflammation
Grandmaternal allergen exposure causes distinct epigenetic trajectories in offspring associated with airway hyperreactivity and inflammation Open
Maternal asthma increases childhood asthma risk through multiple mechanisms including epigenetic regulation of asthma-associated genes. DNA methylation is one form of epigenetic regulation that is both inherited and modified by environment…
View article: Metformin prevents airway hyperreactivity in rats with dietary obesity
Metformin prevents airway hyperreactivity in rats with dietary obesity Open
Increased insulin is associated with obesity-related airway hyperreactivity and asthma. We tested whether the use of metformin, an antidiabetic drug used to reduce insulin resistance, can reduce circulating insulin, thereby preventing airw…
View article: Airway Sensory Nerve Plasticity in Asthma and Chronic Cough
Airway Sensory Nerve Plasticity in Asthma and Chronic Cough Open
Airway sensory nerves detect a wide variety of chemical and mechanical stimuli, and relay signals to circuits within the brainstem that regulate breathing, cough, and bronchoconstriction. Recent advances in histological methods, single cel…
View article: Pioglitazone prevents obesity-related airway hyperreactivity and neuronal M<sub>2</sub> receptor dysfunction
Pioglitazone prevents obesity-related airway hyperreactivity and neuronal M<sub>2</sub> receptor dysfunction Open
Obesity-related asthma often presents with more severe symptoms than non-obesity-related asthma and responds poorly to current treatments. Both insulin resistance and hyperinsulinemia are common in obesity. We have shown that increased ins…
View article: Airway Reactivity to Optogenetic Parasympathetic Nerve Stimulation Is Enhanced by Acute but Not Chronic Eosinophilia in Mice
Airway Reactivity to Optogenetic Parasympathetic Nerve Stimulation Is Enhanced by Acute but Not Chronic Eosinophilia in Mice Open
Rationale: Airway parasympathetic nerves provide the dominant control of airway tone.To study airway parasympathetic nerve-mediated bronchoconstriction in vivo, we developed an optogenetic mouse strain that expresses channelrhodopsin 2 dri…
View article: TLR7&nbsp;Is Expressed by Support Cells, but Not Sensory Neurons, in Ganglia&nbsp;
TLR7 Is Expressed by Support Cells, but Not Sensory Neurons, in Ganglia Open
Background: Toll like receptor 7 (TLR7) is an innate immune receptor that detects viral single-stranded RNA and triggers production of proinflammatory cytokines and type 1 interferons in immune cells. TLR7 agonists also modulate sensory ne…
View article: Eosinophil peroxidase induces inflammation in a mouse model of dermatitis
Eosinophil peroxidase induces inflammation in a mouse model of dermatitis Open
Eosinophils play an important role in mediating itch and inflammation in dermatitis. The role of the eosinophil granule protein eosinophil peroxidase (EPX) in mediating inflammation and itch was tested in a dermatitis mouse model. Mice wer…
View article: Transient receptor potential ankyrin-1 causes rapid bronchodilation via nonepithelial PGE<sub>2</sub>
Transient receptor potential ankyrin-1 causes rapid bronchodilation via nonepithelial PGE<sub>2</sub> Open
Transient receptor potential ankyrin-1 (TRPA1) is a ligand-gated cation channel that responds to endogenous and exogenous irritants. TRPA1 is expressed on multiple cell types throughout the lungs, but previous studies have primarily focuse…
View article: Inflammatory mechanisms linking maternal and childhood asthma
Inflammatory mechanisms linking maternal and childhood asthma Open
Asthma is a chronic inflammatory airway disease characterized by airway hyperresponsiveness, inflammation, and remodeling. Asthma often develops during childhood and causes lifelong decrements in lung function and quality of life. Risk fac…
View article: Optogenetic Control of Airway Cholinergic Neurons <i>In Vivo</i>
Optogenetic Control of Airway Cholinergic Neurons <i>In Vivo</i> Open
Dysregulation of airway nerves leads to airway hyperreactivity, a hallmark of asthma. Although changes to nerve density and phenotype have been described in asthma, the relevance of these changes to nerve function has not been investigated…
View article: IL-5 Exposure <i>In Utero</i> Increases Lung Nerve Density and Airway Reactivity in Adult Offspring
IL-5 Exposure <i>In Utero</i> Increases Lung Nerve Density and Airway Reactivity in Adult Offspring Open
Asthma is characterized by airway hyperreactivity and inflammation. In the lungs, parasympathetic and sensory nerves control airway tone and induce bronchoconstriction. Dysregulation of these nerves results in airway hyperreactivity. Human…
View article: Lung eosinophils increase vagus nerve-mediated airway reflex bronchoconstriction in mice
Lung eosinophils increase vagus nerve-mediated airway reflex bronchoconstriction in mice Open
Eosinophils mediate airway hyperresponsiveness by increasing vagally mediated reflex bronchoconstriction. Here, we tested whether circulating or airway eosinophils change nerve function. Airway resistance in response to aerosolized 5-hydro…