Prediction of clinical peanut allergy status among children in Hamilton, Ontario using chart review data collected during 2012-2015.

Background: Peanut sensitization does not necessarily indicate clinical peanut allergy, and uncertainty as to whether or not there is true peanut allergy can lead to increased anxiety and decreased quality of life for patients and their families. The gold standard for diagnosing clinical peanut allergy is the oral food challenge, but this method is time-consuming and can cause severe allergic reactions. It would therefore be beneficial to develop a tool for predicting clinical peanut allergy in peanut-sensitized individuals whose peanut allergy status is unknown so as to better determine who requires an oral food challenge for diagnosis.

Therapeutic potential of anti-IL-6 therapies for granulocytic airway inflammation in asthma.

Background: Determining the cellular and molecular phenotypes of inflammation in asthma can identify patient populations that may best benefit from targeted therapies. Although elevated IL-6 and polymorphisms in IL-6 signalling are associated with lung dysfunction in asthma, it remains unknown if elevated IL-6 levels are associated with a specific cellular inflammatory phenotype, and how IL-6 blockade might impact such inflammatory responses.

Methods: Patients undergoing exacerbations of asthma were phenotyped according to their airway inflammatory characteristics (normal cell count, eosinophilic, neutrophilic, mixed granulocytic), sputum cytokine profiles, and lung function.

Indigenous enteric eosinophils control DCs to initiate a primary Th2 immune response in vivo.

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, and Th2 priming was restored by reconstitution with il4(+/+) or il4(-/-) eosinophils. Eosinophils controlled CD103(+) dendritic cell (DC) activation and migration from the intestine to draining lymph nodes, events necessary for Th2 priming.

A GM-CSF/IL-33 pathway facilitates allergic airway responses to sub-threshold house dust mite exposure.

Allergic asthma is a chronic immune-inflammatory disease of the airways. Despite aeroallergen exposure being universal, allergic asthma affects only a fraction of individuals. This is likely related, at least in part, to the extent of allergen exposure.

IL-33, but not thymic stromal lymphopoietin or IL-25, is central to mite and peanut allergic sensitization.

Background: Allergen exposure at lung and gut mucosae can lead to aberrant T(H)2 immunity and allergic disease. The epithelium-associated cytokines thymic stromal lymphopoietin (TSLP), IL-25, and IL-33 are suggested to be important for the initiation of these responses.

Objective: We sought to investigate the contributions of TSLP, IL-25, and IL-33 in the development of allergic disease to the common allergens house dust mite (HDM) or peanut.

Eosinophils are dispensable for allergic remodeling and immunity in a model of house dust mite-induced airway disease.

Rationale: Current thinking accredits eosinophils with preeminent contributions to allergic airway responses, including a major role in the development of airway remodeling, a process thought to significantly contribute to airway dysfunction. However, direct evidence in support of this notion is limited and often controversial.

Objectives: We elucidated the requirement for eosinophils in the generation of allergic sensitization, airway inflammation, and remodeling in a model involving chronic respiratory exposure to house dust mite (HDM).

Concurrent blockade of platelet-activating factor and histamine prevents life-threatening peanut-induced anaphylactic reactions.

Background: Food anaphylaxis is an acute and life-threatening systemic allergic reaction. Fatality registries place peanut as the most common culprit of fatal and near-fatal reactions in North America. Because prophylaxis and treatment have advanced little in recent years, it is imperative to evaluate novel therapies.

Acute, but not resolved, influenza A infection enhances susceptibility to house dust mite-induced allergic disease.

The impact of respiratory viral infections on the emergence of the asthmatic phenotype is a subject of intense investigation. Most experimental studies addressing this issue have used the inert Ag OVA with controversial results. We examined the consequences of exposure to a low dose of the common aeroallergen house dust mite (HDM) during the course of an influenza A infection.

In vivo-to-in silico iterations to investigate aeroallergen-host interactions.

Background: Allergic asthma is a complex process arising out of the interaction between the immune system and aeroallergens. Yet, the relationship between aeroallergen exposure, allergic sensitization and disease remains unclear. This knowledge is essential to gain further insight into the origin and evolution of allergic diseases.

Transforming growth factor-beta regulates house dust mite-induced allergic airway inflammation but not airway remodeling.

Rationale: It is now believed that both chronic airway inflammation and remodeling contribute significantly to airway dysfunction and clinical symptoms in allergic asthma. Transforming growth factor (TGF)-beta is a powerful regulator of both the tissue repair and inflammatory responses, and numerous experimental and clinical studies suggest that it may play an integral role in the pathogenesis of asthma.

Objectives: We investigated the role of TGF-beta in the regulation of allergic airway inflammation and remodeling using a mouse model of house dust mite (HDM)-induced chronic allergic airway disease.

Impact of CD40 ligand, B cells, and mast cells in peanut-induced anaphylactic responses.

The effector immune mechanisms underlying peanut-induced anaphylaxis remain to be fully elucidated. We investigated the relative contribution of Igs, mast cells (MCs), and FcepsilonRI in the elicitation of anaphylaxis in a murine model. Assessment of peanut hypersensitivity reactions was performed clinically and biologically.

House dust mite facilitates ovalbumin-specific allergic sensitization and airway inflammation.

Rationale: Mouse models of allergic airway disease have greatly contributed to our understanding of disease induction and pathogenesis. Although these models typically investigate responses to a single antigen or allergen, humans are frequently exposed to a myriad of allergens, each with distinct antigenic potential.

Objectives: Given that airway exposure to ovalbumin (OVA), a prototypic innocuous antigen, induces inhalation tolerance, we wished to investigate how this response would be altered if OVA were encountered concurrently with a house dust mite extract (HDM), which we have recently shown is capable of eliciting a robust allergic airway inflammatory response that is mediated, at least in part, by granulocyte-macrophage colony-stimulating factor.

B7RP-1 is not required for the generation of Th2 responses in a model of allergic airway inflammation but is essential for the induction of inhalation tolerance.

The recently described ICOS-B7RP-1 costimulatory pathway has been implicated in the generation of effector Th2 responses and, hence, has become an attractive therapeutic target for allergic diseases. In the present study, we used B7RP-1-deficient mice to investigate the role of B7RP-1 in the generation and maintenance of Th2 responses in a model of mucosal allergic airway inflammation. We found that exposure of B7RP-1 knockout mice to aerosolized OVA in the context of GM-CSF leads to airway eosinophilic inflammation.

Cutaneous antigen priming via gene gun leads to skin-selective Th2 immune-inflammatory responses.

It is becoming increasingly evident that the compartmentalization of immune responses is governed, in part, by tissue-selective homing instructions imprinted during T cell differentiation. In the context of allergic diseases, the fact that "disease" primarily manifests in particular tissue sites, despite pervasive allergen exposure, supports this notion. However, whether the original site of Ag exposure distinctly privileges memory Th2 immune-inflammatory responses to the same site, while sparing remote tissue compartments, remains to be fully investigated.

Intranasal exposure of mice to house dust mite elicits allergic airway inflammation via a GM-CSF-mediated mechanism.

It is now well established that passive exposure to inhaled OVA leads to a state of immunological tolerance. Therefore, to elicit allergic sensitization, researchers have been compelled to devise alternative strategies, such as the systemic delivery of OVA in the context of powerful adjuvants, which are alien to the way humans are exposed and sensitized to allergens. The objectives of these studies were to investigate immune-inflammatory responses to intranasal delivery of a purified house dust mite (HDM) extract and to evaluate the role of GM-CSF in this process.

Impact of cigarette smoke on clearance and inflammation after Pseudomonas aeruginosa infection.

The object of this study was to investigate the impact of cigarette smoke on bacterial clearance and immune inflammatory parameters after infection with Pseudomonas aeruginosa in mice. We observed a delayed rate of bacterial clearance in smoke-exposed compared with sham-exposed mice. This was associated with increased inflammation characterized by greater numbers of neutrophils and mononuclear cells in the bronchoalveolar lavage.

Transient corticosteroid treatment permanently amplifies the Th2 response in a murine model of asthma.

Corticosteroids (CS) remain the most efficacious pharmacotherapeutic option for the management of asthma. Although the acute anti-inflammatory effects of CS treatment have been amply documented both clinically and experimentally, recent human data intimate that exposure to CS may be associated with retrograde immune phenomena, including enhanced synthesis of IgE in vivo and elevated Th2 cytokine production in vitro. We have investigated the long-term immunologic effects of CS treatment in a murine model of allergic airway inflammation.

Cigarette smoke decreases pulmonary dendritic cells and impacts antiviral immune responsiveness.

We investigated the impact of cigarette smoke exposure on respiratory immune defense mechanisms. Mice were exposed to two cigarettes daily, 5 d/wk, for 2-4 mo. Tobacco smoke decreased the number of dendritic cells (DCs) in the lung tissue.

Evaluation of inducible costimulator/B7-related protein-1 as a therapeutic target in a murine model of allergic airway inflammation.

Given its primary role in the execution of T cell, and especially Th2, effector activity, the inducible costimulator (ICOS)/B7-related protein (RP)-1 costimulatory pathway is currently being heralded as a promising therapeutic target for immune-inflammatory disorders such as asthma. This study investigates the merits of ICOS blockade in a murine model of experimental asthma in which mice are sensitized to ovalbumin (OVA) through the respiratory mucosa. Intraperitoneal treatment of mice with anti-ICOS neutralizing antibody during sensitization resulted in a marked reduction in airway eosinophilia and IL-5 in bronchoalveolar lavage, but had no effect on interleukin (IL)-4, IL-13, and eotaxin content in bronchoalveolar lavage or the production of OVA-specific immunoglobulin E in serum.

Effect of GM-CSF on immune, inflammatory, and clinical responses to ragweed in a novel mouse model of mucosal sensitization.

Background: Conventional models of allergic airway inflammation involve intraperitoneal administration of ovalbumin in conjunction with a chemical adjuvant (generally aluminum hydroxide) to generate allergic airways inflammation. Here we have investigated the effect of respiratory mucosal exposure to a ragweed extract in the absence of chemical adjuvant on the generation of allergic responses.

Objectives: We sought to develop a mouse model of ragweed-induced allergic airway inflammation through mucosal sensitization and to investigate the role of GM-CSF in this process.