IL-25 and IL-33 induce Type 2 inflammation in basophils from subjects with allergic asthma

Salter, Brittany; Oliveria, John Paul; Nusca, Graeme; Smith, Steven G; Tworek, Damian; Mitchell, Patrick; Watson, Rick; Sehmi, Roma; Gauvreau, Gail M.

doi:10.1186/s12931-016-0321-z

Cited by 64 publications

(63 citation statements)

References 43 publications

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“…Sputum samples were induced using hypertonic saline and mucous plugs were selected from samples followed by disbursement with DPBS, as previously described [30]. In brief, sputum samples were centrifuged at 790 g at 4°C for 10 min, followed by the collection of supernatant, centrifugation at 1,500 g at 4°C for 10 min, and aliquoting of supernatant into Eppendorf tubes that were frozen at –20°C.…”

Section: Methodsmentioning

confidence: 99%

IL-33 and Its Receptor ST2 after Inhaled Allergen Challenge in Allergic Asthmatics

Mitchell

Salter

Oliveria

et al. 2018

Int Arch Allergy Immunol

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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 unclear. Objective: The aim of this work was to evaluate in vitro the effect of allergen inhalation on IL-33 levels and expression of its receptor (ST2L) on eosinophils in allergic asthmatics, and the effect of IL-33 stimulation on eosinophil activity. Methods: Plasma and sputum IL-33, soluble ST2 (sST2) levels, and ST2L expression on eosinophils were measured in 10 healthy controls and 10 allergic asthmatics. Asthmatics underwent allergen and diluent inhalation challenges. Blood and sputum samples were collected to measure IL-33, sST2, and ST2L eosinophil expression before and 24 h after allergen inhalation. Purified blood eosinophils from allergic asthmatics were incubated overnight with IL-33 to assess ST2 and intracellular IL-5 expression. Results: Baseline levels of IL-33 in sputum and sST2 in plasma and sputum were similar in allergic asthmatics compared to healthy controls. In addition, there was no difference in blood or sputum eosinophil ST2L expression in healthy controls versus allergic asthmatics. Eosinophil ST2L expression was significantly increased 24 h postallergen inhalation in allergic asthmatics. In vitro stimulation of human eosinophils with IL-33 and LPS significantly increased eosinophil ST2L expression and IL-33 stimulation increased intracellular IL-5 expression, which was attenuated by treatment with sST2 and ST2 blockade. Conclusion and Clinical Relevance: In mild asthmatics, there was a significant upregulation of ST2 surface expression on eosinophils from blood and sputum following allergen inhalation challenge. In vitro, IL-33 stimulation of eosinophils increases both ST2 membrane expression and IL-5 production. These results support a role for IL-33 in causing allergen-induced eosinophilia. Blockade of IL-33 and ST2 signaling may present a novel therapeutic avenue for asthma treatment.

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Section: Methodsmentioning

confidence: 99%

IL-33 and Its Receptor ST2 after Inhaled Allergen Challenge in Allergic Asthmatics

Mitchell

Salter

Oliveria

et al. 2018

Int Arch Allergy Immunol

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“…IL-25 is able to induce promotion of the T H 2 lineage via activation of DCs [35] and is involved in the proliferation of a subpopulation of inflammatory ILC2s [36]. Finally, IL-33 and IL-25 also increase basophil activation and migration in allergic asthma patients [37], and high levels of both cytokines have been reported in bronchoalveolar lavage fluid in asthma models [38].…”

Section: Airway Epithelium As a Key Player In Orchestrating The Allermentioning

confidence: 99%

Airway Epithelium Plays a Leading Role in the Complex Framework Underlying Respiratory Allergy

López-Rodríguez

Benedé

Barderas

et al. 2017

J Investig Allergol Clin Immunol

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Airway epithelium is the cellular structure with the greatest surface exposed to a plethora of environmental airborne substances, including microorganisms, respiratory viruses, air pollutants, and allergens. In addition to being a protective physical barrier at the air-liquid interface, the airway epithelium acts as an effective chemical and immunological barrier that plays a crucial role in orchestrating the immune response in the lungs, by supporting the activation, recruitment, and mobilization of immune cells. Airway epithelium dysfunction has been clearly associated with various airway inflammatory diseases, such as allergic asthma. Although it is not fully understood why a person develops respiratory allergy, a growing body of evidence shows that the nature of the host's immune response is strongly determined by the state of the airway epithelium at the time of contact with the inhaled allergen. Our review highlights the physiological state of airway epithelium as a key element in the development of allergy and, particularly, in exacerbation of asthma. We review the role of physiological oxidants as signaling molecules in lung biology and allergic diseases and examine how high exposure to air pollutants (eg, cigarette smoke and diesel particles) can contribute to the increased incidence of respiratory allergy and exacerbation of the disease. Key words: Airway epithelium. Barrier dysfunction. Respiratory allergy. Redox biology. Air pollutants. ResumenEl epitelio pulmonar constituye la barrera celular más susceptible a la acción deletérea de la multitud de agentes que se encuentran en el ambiente, incluidos los alérgenos. Además de prevenir su acceso al organismo, la barrera epitelial de las vías respiratorias juega un papel inmunomodulador crucial, regulando de forma local la acción de las células del sistema inmune subyacentes. Una disfunción epitelial, provocada tanto directa como indirectamente por la acción de los aeroalérgenos, parece ser una de las causas principales de desregulación de la homeostasis pulmonar, causando una respuesta proinflamatoria descontrolada que cada vez más autores atribuyen al origen de las reacciones alérgicas. En esta revisión se quiere destacar el papel de la barrera epitelial pulmonar como regulador de la respuesta inmune en el contexto de la alergia. Las enfermedades crónicas que afectan a las vías respiratorias, tales como el asma alérgica, muestran frecuentemente una función epitelial defectuosa, apoyando así la hipótesis antes mencionada que subyace al origen de la alergia. El impacto de otros contaminantes ambientales -como virus respiratorios, bacterias, humo del tabaco y partículas diésel-sobre la integridad epitelial, así como su influencia en la biología redox pulmonar relacionada con el desarrollo de la respuesta alérgica, también se abordarán en la presente revisión.

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“…It has been shown that allergen provocation is able to increase the expression of IL-25 and its receptor in the asthmatic bronchial mucosa [16] and also the expression of the TSLP receptor on the basophil membrane [9]. Salter et al [8] investigated the effects of the alarmin cytokines IL-25 and IL-33 on basophils in a model of allergic asthma, and found that they increase basophil activation and migratory potential. In our patients, the overexpression of IL-25 and IL-33 on basophils was independent of atopy, which suggests causes other than allergy.…”

Section: Discussionmentioning

confidence: 99%

“…Basophils have an important role in the development of airway inflammation, commonly found in bronchial biopsies of asthmatic patients where their number has been reported to be significantly higher than in healthy subjects [7]. Experimental data show that IL-25, IL-33, and TSLP upregulate the expression of their receptors on the basophil membrane [8,9].…”

Section: Introductionmentioning

confidence: 99%

Basophil Membrane Expression of Epithelial Cytokine Receptors in Patients with Severe Asthma

Boita

Heffler²,

Omedè³

et al. 2018

Int Arch Allergy Immunol

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Background: Severe asthma is a heterogeneous disease, which is characterized by airway damage and remodeling. All triggers of asthma, such as allergens, bacteria, viruses, and pollutants, interact with the airway epithelial cells, which drive the airway inflammatory response through the release of cytokines, particularly IL-25, IL-33, and thymic stromal lymphopoietin (TSLP). Objectives and Methods: To investigate whether the expression of the IL-25, IL-33, and TSLP receptors on the basophil membrane are associated with asthma severity. Twenty-six patients with asthma (11 severe and 15 moderate/mild) and 10 healthy subjects (controls) were enrolled in the study. The results of the basophil activation test and flow cytometry analysis were assessed to investigate basophil membrane expression of IL-25, TSLP, and IL-33 receptors before and after IgE stimulation. Results: IL-25 and IL-33 receptor expression on the basophil membrane at baseline were significantly higher in patients with severe asthma than in those with mild/moderate asthma or healthy subjects, independent of atopy, eosinophilia, asthma control, and exacerbation frequency. Following IgE stimulation, a significantly higher increase in the IL-25 and IL-33 receptors was observed in mild/moderate versus severe asthma. Conclusions: The high expression of the IL-25 and IL-33 receptors on the basophil membrane of patients with severe asthma indicates an overstimulation of basophils by these cytokines in severe asthma. This finding can possibly be used as a biomarker of asthma severity.

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IL-25 and IL-33 induce Type 2 inflammation in basophils from subjects with allergic asthma

Cited by 64 publications

References 43 publications

IL-33 and Its Receptor ST2 after Inhaled Allergen Challenge in Allergic Asthmatics

IL-33 and Its Receptor ST2 after Inhaled Allergen Challenge in Allergic Asthmatics

Airway Epithelium Plays a Leading Role in the Complex Framework Underlying Respiratory Allergy

Basophil Membrane Expression of Epithelial Cytokine Receptors in Patients with Severe Asthma

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