Steven Smith

McMaster University | McMaster · Department of Medicine

Background: In severe asthmatics with persistent airway eosinophilia, blockade of interleukin-5 has significant steroid-sparing effects and attenuates blood and sputum eosinophilia. The contribution of local maturational processes of progenitors within the airways relative to the recruitment of mature cells from the peripheral circulation to the d...

The beta common-signaling cytokines interleukin (IL)-3, granulocyte-macrophage colony stimulating factor (GM-CSF) and IL-5 stimulate pro-inflammatory activities of hematopoietic cells via a receptor complex incorporating cytokine-specific alpha and shared beta common (βc, CD131) receptor. Evidence from animal models and recent clinical trials demon...

Background: In patients with severe eosinophilic asthma, local maturation rather than systemic recruitment of mature cells might contribute to persistent airway eosinophilia. Group 2 innate lymphoid cells (ILC2s) are a major source of type 2 cytokines (IL-5 and IL-13) and can facilitate eosinophilic inflammatory responses in mouse models of asthma...

PPARγ agonists can either enhance or inhibit eosinophil migration, which is a sum of directional migration (chemotaxis) and random cell movement (chemokinesis). To date, the effects of PPAR agonists on chemokinesis have not been examined. This study investigates the effects of PPARα, δ, and γ agonists on eosinophil migration and chemokinesis. Eosin...

Background Eosinophil-lineage committed progenitor cells (EoP) migrate from the bone marrow and differentiate locally to provide an ongoing source of mature eosinophils in asthmatic inflammatory responses in the airways. Sputum levels of EoP are increased in asthmatics compared to normal controls suggesting an exaggerated eosinophilopoietic environ...

Background: Previous murine models have demonstrated interleukin (IL)-33 to be an important mediator of type-2 inflammation and to promote airway hyperresponsiveness in allergic asthma. A number of inflammatory cells produce IL-33 and eosinophils express ST2 mRNA. The relationship between IL-33 and eosinophils in allergic asthma, however, remains...

Rationale: Activated bronchial epithelial cells release alarmins, including thymic stromal lymphopoietin (TSLP) that drive type 2 inflammatory responses. We hypothesize that bronchial epithelial-derived factors enhance in situ eosinophil differentiation and maturation from myeloid precursors, a process that is driven by an IL-5 rich micro-environm...

Rationale: Group 2 innate lymphoid cells (ILC2), a major source of type 2 cytokines, initiate eosinophilic inflammatory responses in murine models of asthma. Objectives: Investigate the role of ILC2 in allergen-induced airway eosinophilic responses in atopic asthmatics. Methods: Using a diluent-controlled allergen challenge cross-over study, w...

Background: The alarmin cytokines IL-25 and IL-33 are key promoters of type 2 inflammation. Basophils respond to alarmin cytokines, however the relationship of these cytokines with basophil activation and recruitment in human studies of allergic asthma has not been well characterized. This study investigated the effect of IL-25 and IL-33 on basoph...

Background: Glucagon-like peptide-1 (GLP-1) and its receptor are part of the incretin family of hormones that regulate glucose metabolism. GLP-1 also has immune modulatory roles. Objectives: To measure the expression of the GLP-1 receptor (GLP-1R) on eosinophils and neutrophils in normal and asthmatic subjects and evaluate effects of a GLP-1 ana...

Background: Interleukin (IL)-25 plays a pivotal role in type 2 immune responses. In a baseline cross-sectional study, we previously showed that IL-25 plasma levels and IL-25 receptor (IL-25R: IL-17RA, IL-17RB, and IL-17RA/RB) expression on mature blood eosinophils are increased in atopic asthmatics compared to normal nonatopic controls. This study...

Table of contents A1 Role of fibrocytes in allergic rhinitis Marie-Ève Côté, Marie-Ève Boulay, Sophie Plante, Jamila Chakir, Louis-Philippe Boulet A2 Patterns of aeroallergens sensitization in Northern Alberta Hanan Ahmed, Maria-Beatriz Ospina, Kyriaki Sideri, Harissios Vliagoftis A3 Addressing acceptable risk for adolescents with Food-Induced Anap...

Background: Dendritic cells (DCs) are antigen presenting cells essential for the initiation of T-cell responses. Allergen inhalation increases the number of airway DCs and the release of epithelial-derived cytokines, such as interleukin (IL)-33 and thymic stromal lymphopoietin (TSLP), that activate DCs. Objectives: To examine the effects of inha...

Rationale: Interleukin (IL)-25 is an epithelial-derived cytokine, whose effects are mediated by the IL-25 receptor (IL-17RB), and which has been implicated in the pathogenesis of allergic disease and airway viral responses. Airway myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs) are professional antigen-presenting cells. pDCs...

Background: Interleukin (IL)-25plays a pivotal role in the maintenance of eosinophil and T-helper (Th)2 dominate allergic responses like asthma. We previously demonstrated that plasma IL-25 levels and IL-25 receptor (IL-17RB and IL-17RA) expression on eosinophils are increased in allergic asthmatics compared with atopic non-asthmatics and normal su...

OX40-OX40L interactions and TSLP are important in the induction and maintenance of Th2 responses in allergic disease whereas T regulatory cells (Treg) have been shown to suppress pro-inflammatory Th2 responses. Both OX40L and TSLP have been implicated in the negative regulation of Treg. The effect of anti-asthma therapies on Treg is not well known....

An unresolved issue in T regulatory (Treg) cell biology is the lack of consensus on phenotypic markers that accurately define the natural Treg (nTreg) population. To examine nTreg frequency and functional capacity in healthy controls, and their frequency in asthmatic subjects using three different phenotypic strategies. We hypothesized that phenoty...

Thymic stromal lymphopoietin (TSLP) released after antigenic stimulation of allergic asthmatic airways is a key initiator of type 2 inflammation. Basophils are important effectors of allergic inflammation in the airways. Murine basophils have been shown to respond to TSLP independently of IL-3 by increasing functional thymic stromal lymphopoietin r...

Thymic stromal lymphopoietin (TSLP) and IL-33 are considered important initiators of type 2 immunity. In asthmatic patients allergic inflammatory responses are associated with increased lung homing of bone marrow-derived CD34(+) hematopoietic progenitor cells (HPCs), which include eosinophil lineage-committed progenitor cells. In this study we inve...

Background: T helper (Th)17 cells may play a role in allergic asthma. This study assessed the effect of allergen inhalation challenge on circulating Th17 cells and related cytokines in allergic asthmatics. Methods: Peripheral blood mononuclear cells were collected from 16 atopic asthmatics before and 24 h after allergen challenge, as well as fro...

Nicotinic acetylcholine receptors (nAChRs) were identified on eosinophils and shown to regulate inflammatory responses, but nAChR expression on basophils has not been explored yet. We investigated surface receptor expression of nAChR α4, α7 and α1/α3/α5 subunits on basophils. Furthermore, we examined the effects of ASM-024, a synthetic nicotinic li...

PurposePPAR agonists have been suggested as novel therapeutics for the treatment of inflammatory lung disease, such as allergic asthma. Treatment with PPAR agonists have been shown to inhibit airway eosinophilia in murine models of allergic asthma, which can occur through several mechanisms including attenuated generation of chemoattractants (e.g....

Background: Allergic asthma is an inflammatory airway disease in which Th2 cytokines play an important role. Epithelial-derived interleukin (IL)-25 has been suggested to be important in the maintenance of Th2-type responses. The effects of IL-25 are mediated by the IL-25 receptor, composed of two subunits, IL-17RA and IL-17RB. Eosinophils are effe...

Natural regulatory T (Treg) cells are implicated in the regulation of the inflammatory response in patients with allergic asthma. We sought to determine changes in Treg cell numbers in the airways and peripheral blood of isolated early responder (IER) versus dual responder (DR) subjects with mild allergic asthma before and after allergen challenge....

Myeloid dendritic cells type 2 (mDC2s) are a new subtype of DCs identified in both the circulation and the lung and suggested to have a role in allergic asthma. Circulating mDC2s were enumerated in 19 healthy, 18 atopic nonasthmatic, 18 mild atopic asthmatic, and 16 moderate/severe atopic asthmatic subjects using flow cytometry. The number of circu...

Introduction: Asthma is an inflammatory disease, which can be exacerbated by stimuli such as viral infections and exposure to allergens. Asthma continues to be a profound public health problem due to asthma exacerbation in a low proportion of patients in need of more effective medications. Areas covered: The C5 complement pathway has been propos...

Induced sputum is used to assess markers of inflammation in asthmatic individuals, and sputum cell differential counts provide an outcome to evaluate the presence, type, and degree of inflammation in the airways. Contamination of sputum slides with squamous epithelial cells (SECs) has been reported to adversely affect the reproducibility of sputum...

Lung-homing of progenitor cells is associated with inflammatory and remodelling changes in asthma. Factors that modulate the increased traffic of progenitor cells to the site of inflammation in asthma remain to be defined. Interleukin (IL)-4 and IL-13 are Th2 cytokines that are key regulators of asthma pathology. We investigated the role of IL-4 an...

To the Editors: The inflammatory process in allergic asthma is initiated by T-helper (Th) type-2 cells, which produce a repertoire of cytokines, including interleukin (IL)-4, IL-5, IL-9 and IL-13, which are necessary for immunoglobulin (Ig)E production, airway eosinophilia and goblet cell hyperplasia [1]. IL-18 is another pro-inflammatory cytokine...

Evaluation of: Bree A, Schlerman FJ, Wadanoli M et al. IL-13 blockade reduces lung inflammation after Ascaris suum challenge in cynomolgus monkeys. J. Allergy Clin. Immunol. 119, 1251-1257 (2007). There is abundant evidence supporting IL-13 as having a central role in the pathology of allergic asthma. IL-13 induces immunological responses relevant...