The role of IL‐33 and mast cells in allergy and inflammation

Saluja, Rohit; Khan, Mahejibin; Church, Martin K.; Maurer, Marcus

doi:10.1186/s13601-015-0076-5

Cited by 174 publications

(133 citation statements)

References 79 publications

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“…IL-33 is an “epithelial-derived” cytokine that promotes type 2–associated immune responses and has been strongly linked to allergy (8). Upon IL-33–mediated activation, mast cells have been shown to exhibit enhanced adhesion, survival, maturation, and production of several pro-inflammatory cytokines (9, 10). In basophils, IL-33–mediated activation has been described as promoting migration towards eotaxin and enhancing degranulation upon concurrent IgE-mediated activation (11).…”

Section: Introductionmentioning

confidence: 99%

Transcriptional Heterogeneity of Mast Cells and Basophils upon Activation

Chhiba

Hsu

Berdnikovs

et al. 2017

The Journal of Immunology

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Mast cells and basophils are developmentally related cells whose activation is a hallmark of allergy. Functionally, mast cells and basophils overlap in their ability to produce several mediators, including histamine and granule proteases, but studies have increasingly demonstrated non-redundant roles. To characterize the transcriptional heterogeneity of mast cells and basophils upon their activation, we performed large-scale comparative microarrays of murine bone marrow–derived mast cells (BMMCs) and basophils (BMBs) at rest, upon an adaptive-type activation (IgE crosslinking), or upon an innate-type activation (IL-33 stimulation). Hierarchical clustering demonstrated that BMMCs and BMBs shared specific activation-associated transcriptional signatures but differed in others, both between cell type and between activation mode. In BMMCs, IgE crosslinking upregulated 785 genes including Egr2, Ccl1, and Fxyd6, while IL-33 stimulation induced 823 genes including Ccl1, Egr2, and Il1b. Focused bioinformatics pathway analysis demonstrated that IgE activation aligned with processes such as oxidative phosphorylation, angiogenesis, and the p53 pathway. The IL-33–activated transcriptome was enriched in genes commonly altered by NF-κB in response to TNF, by IL-6 via STAT3, and in response to IFNγ. Furthermore, BMBs activated via IgE crosslinking selectively induced immune response genes Ccl1, Il3, and Il2 compared to IL-33–stimulated BMBs. Principal-component analysis revealed key cell- and activation-specific clustering. Overall, our data demonstrate that mast cells and basophils have cell- and activation-specific transcriptional responses and suggest that context-specific gene networks and pathways may shape how the immune system responds to allergens and innate cytokines.

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Section: Introductionmentioning

confidence: 99%

Transcriptional Heterogeneity of Mast Cells and Basophils upon Activation

Chhiba

Hsu

Berdnikovs

et al. 2017

The Journal of Immunology

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“…They differ in their mast cell-activating triggers, but are similar in that histamine and other inflammatory mast cell mediators are involved in their pathogenesis. Both disorders include the involvement of cytokines/mediators such as IL-4, IL10, IL-33 and B cell-activating factor (BAFF) - all of which contribute to the activation of many immune cells and the influx of leukocytes to the dermis and airways [1,2,3]. In both conditions, IgE is frequently elevated and anti-IgE therapy is highly effective.…”

Section: Introductionmentioning

confidence: 99%

Seasonal Exacerbation of Asthma Is Frequently Associated with Recurrent Episodes of Acute Urticaria

Vadasz

Kessel

Hershko

et al. 2016

Int Arch Allergy Immunol

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Background: Asthma and urticaria are both partially mediated by an increased release of histamine from highly activated mast cells. They are pathophysiologically different, as mast cell degranulation in these 2 disorders results from different mechanisms. Objective: To assess the incidence of urticaria in patients with asthma, and of asthma in patients with chronic spontaneous urticaria (CSU). Patients and Methods: Over 1 year of follow-up, asthma patients (n = 110) were assessed for the incidence and characteristics of urticaria, and a link, if it existed, to seasonal exacerbations and the severity of asthma was traced. We also prospectively assessed CSU patients (n = 95) during the same period of time for the incidence of asthma. Healthy individuals (n = 100), serving as a control group, were also assessed. Results: Episodes of urticaria occurred in 26/110 asthma patients (23.6%), but in only 2/100 healthy control subjects (2%) (p < 0.0001). During the 1-year observation period, episodes of urticaria were significantly more frequent in asthma patients with positive skin-prick test reactions (mainly seasonal pollens), and consequently occurred mostly during seasonal asthma exacerbation, i.e. during acute episodes of urticaria. The incidence of asthma in CSU patients was recorded in 10.5% of the group, similar to that in the healthy control population. Discussion: Our study demonstrates, for the first time, that asthma patients frequently develop acute urticaria, mainly during seasonal exacerbations. In contrast, CSU patients do not show an increased incidence of asthma.

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“…Ultimately, the crosstalk between immune and structural cells creates a chronic inflammatory environment which might be the major cause of the airway changes commonly observed in patients with severe asthma. Several studies have shown that IL-33 is expressed more abundantly in asthma patients than in healthy individuals [21][22][23]. Additionally, immunohistochemistry studies have reported elevated IL-33 expression in the bronchial epithelial cells of asthma patients versus healthy individuals [24].…”

Section: Discussionmentioning

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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The role of IL‐33 and mast cells in allergy and inflammation

Cited by 174 publications

References 79 publications

Transcriptional Heterogeneity of Mast Cells and Basophils upon Activation

Transcriptional Heterogeneity of Mast Cells and Basophils upon Activation

Seasonal Exacerbation of Asthma Is Frequently Associated with Recurrent Episodes of Acute Urticaria

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

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