Dataset Information

Glucagon-like peptide 1 signaling inhibits allergen-induced lung IL-33 release and reduces group 2 innate lymphoid cell cytokine production in vivo.

ABSTRACT:

Background

IL-33 is one of the most consistently associated gene candidates for asthma identified by using a genome-wide association study. Studies in mice and in human cells have confirmed the importance of IL-33 in inducing type 2 cytokine production from both group 2 innate lymphoid cells (ILC2s) and T_H2 cells. However, there are no pharmacologic agents known to inhibit IL-33 release from airway cells.

Objective

We sought to determine the effect of glucagon-like peptide 1 receptor (GLP-1R) signaling on aeroallergen-induced airway IL-33 production and release and on innate type 2 airway inflammation.

Methods

BALB/c mice were challenged intranasally with Alternaria extract for 4 consecutive days. GLP-1R agonist or vehicle was administered starting either 2 days before the first Alternaria extract challenge or 1 day after the first Alternaria extract challenge.

Results

GLP-1R agonist treatment starting 2 days before the first Alternaria extract challenge decreased IL-33 release in the bronchoalveolar lavage fluid and dual oxidase 1 (Duox1) mRNA expression 1 hour after the first Alternaria extract challenge and IL-33 expression in lung epithelial cells 24 hours after the last Alternaria extract challenge. Furthermore, GLP-1R agonist significantly decreased the number of ILC2s expressing IL-5 and IL-13, lung protein expression of type 2 cytokines and chemokines, the number of perivascular eosinophils, mucus production, and airway responsiveness compared with vehicle treatment. GLP-1R agonist treatment starting 1 day after the first Alternaria extract challenge also significantly decreased eosinophilia and type 2 cytokine and chemokine expression in the airway after 4 days of Alternaria extract challenge.

Conclusion

These results reveal that GLP-1R signaling might be a therapy to reduce IL-33 release and inhibit the ILC2 response to protease-containing aeroallergens, such as Alternaria.

SUBMITTER: Toki S

PROVIDER: S-EPMC9639650 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Publications

Glucagon-like peptide 1 signaling inhibits allergen-induced lung IL-33 release and reduces group 2 innate lymphoid cell cytokine production in vivo.

Toki Shinji S Goleniewska Kasia K Reiss Sara S Zhang Jian J Bloodworth Melissa H MH Stier Matthew T MT Zhou Weisong W Newcomb Dawn C DC Ware Lorraine B LB Stanwood Gregg D GD Galli Aurelio A Boyd Kelli L KL Niswender Kevin D KD Peebles R Stokes RS

The Journal of allergy and clinical immunology 20180110 5

<h4>Background</h4>IL-33 is one of the most consistently associated gene candidates for asthma identified by using a genome-wide association study. Studies in mice and in human cells have confirmed the importance of IL-33 in inducing type 2 cytokine production from both group 2 innate lymphoid cells (ILC2s) and T<sub>H</sub>2 cells. However, there are no pharmacologic agents known to inhibit IL-33 release from airway cells.<h4>Objective</h4>We sought to determine the effect of glucagon-like pept ...[more]

PMID: 29331643

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Project description:Rationale: The major cause of heart failure is myocardium death consequent to detrimental cardiac remodeling and fibrosis following myocardial infarction. The cardiac protective cytokine interleukin (IL)-33, which signals by ST2 receptor binding, is associated with group 2 innate lymphoid cell (ILC2) activation and regulates tissue homeostasis and repair following tissue injury in various tissues. However, the distribution and role of IL-33-responsive ILC2s in cardiac fibrosis remain unclear. In this study, we elucidated the roles of IL-33-responsive cardiac-resident ILC2s and IL-33-mediated immunomodulatory functions in cardiac fibrosis. Methods: We examined the distribution of cardiac ILC2s by using flow cytometry. The roles of IL-33-mediated ILC2 expansion in cardiac fibrosis was evaluated in the mouse model of catecholamine-induced cardiac fibrosis. ILC-deficient Rag2‒/‒IL2Rγc‒/‒ mice were implemented to determine the contribution of endogenous ILC in the progression of cardiac fibrosis. Histopathological assessments, speckle tracking echocardiography, and transcriptome profile analysis were performed to determine the effects of IL-33-mediated cardiac protective functions. Results: We identified the resident cardiac ILC2s, which share similar cell surface marker and transcriptional factor expression characteristics as peripheral blood and lung tissue ILC2s. IL-33 treatment induced ILC2 expansion via ST2. In vivo, ILC-deficient Rag2‒/‒IL2Rγc‒/‒ mice developed exacerbated cardiac fibrosis following catecholamine-induced stress cardiac injury. IL-33 treatment expanded cardiac ILC2s and revealed protective effects against cardiac tissue damage with reduced cardiomyocyte death, immune cell infiltration, tissue fibrosis, and improved myocardial function. Transcriptome analysis revealed that IL-33 attenuated extracellular matrix synthesis- and fibroblast activation-associated gene expressions. IL13-knockout or epidermal growth factor receptor (EGFR) inhibition abolished IL-33-mediated cardiac protective function, confirming IL-13 and EGFR signaling as crucial for IL-33-mediated cardioprotective responses. Moreover, ILC2-produced BMP-7 served as a novel anti-fibrotic factor to inhibit TGF-β1-induced cardiac fibroblast activation. Conclusion: Our findings indicate the presence of IL-33-responsive ILC2s in cardiac tissue and that IL-33-mediated ILC2 expansion affords optimal cardioprotective function via ILC2-derived factors. IL-33-mediated immunomodulation is thus a promising strategy to promote tissue repair and alleviate cardiac fibrosis following acute cardiac injury.

Dataset Information

Glucagon-like peptide 1 signaling inhibits allergen-induced lung IL-33 release and reduces group 2 innate lymphoid cell cytokine production in vivo.

Background

Objective

Methods

Results

Conclusion

Publications

Glucagon-like peptide 1 signaling inhibits allergen-induced lung IL-33 release and reduces group 2 innate lymphoid cell cytokine production in vivo.

Similar Datasets

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