Blockade of IL-33/ST2 ameliorates airway inflammation in a murine model of allergic asthma

Lee, Hea Yon; Rhee, Chin Kook; Kang, Ji Young; Byun, Ji Hae; Choi, Joon Young; Kim, Seung Joon; Kim, Young Kyoon; Kwon, Soon Suk; Lee, Sook Young

doi:10.3109/01902148.2013.870261

Cited by 113 publications

(88 citation statements)

References 38 publications

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“…Although hASC-sST2-based therapy was able to prevent IL-33 induction, the fact that unmodified hASCs already resolved the principal features of the asthmatic pathology in our model would explain the minor enhancement of the beneficial effect observed after hASC-sST2 administration. Thus, additional blockade of the IL-33-T1/ST2 pathway by sustained overexpression of sST2 from the engineered hASCs might be able to abrogate the persistence of AHR, as suggested recently using either this decoy receptor, a monoclonal antibody against IL-33 [37], or a monoclonal antibody against T1/ST2 [38]. It remains to be seen whether hASC-sST2 would be able to further extend the therapeutic benefit provided by unmodified hASCs at later time points after AP challenge.…”

Section: Figmentioning

confidence: 99%

Human Mesenchymal Stem Cells Resolve Airway Inflammation, Hyperreactivity, and Histopathology in a Mouse Model of Occupational Asthma

Martínez-González

Cruz

Moreno

et al. 2014

Stem Cells and Development

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Occupational asthma (OA) is characterized by allergic airway inflammation and hyperresponsiveness, leading to progressive airway remodeling and a concomitant decline in lung function. The management of OA remains suboptimal in clinical practice. Thus, establishing effective therapies might overcome the natural history of the disease. We evaluated the ability of human adipose-tissue-derived mesenchymal stem cells (hASCs), either unmodified or engineered to secrete the IL-33 decoy receptor sST2, to attenuate the inflammatory and respiratory symptoms in a previously validated mouse model of OA to ammonium persulfate (AP). Twenty-four hours after a dermal AP sensitization and intranasal challenge regimen, the animals received intravenously 1 · 10 6 cells (either hASCs or hASCs overexpressing sST2) or saline and were analyzed at 1, 3, and 6 days after treatment. The infused hASCs induced an anti-inflammatory and restorative program upon reaching the APinjured, asthmatic lungs, leading to early reduction of neutrophilic inflammation and total IgE production, preserved alveolar architecture with nearly absent lymphoplasmacytic infiltrates, negligible smooth muscle hyperplasia/hypertrophy in the peribronchiolar areas, and baseline airway hyperreactivity (AHR) to methacholine. Local sST2 overexpression barely increased the substantial efficacy displayed by unmodified hASCs. Thus, hASCs may represent a viable multiaction therapeutic capable to adequately respond to the AP-injured lung environment by resolving inflammation, tissue remodeling, and bronchial hyperresponsiveness typical of OA.

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Section: Figmentioning

confidence: 99%

Human Mesenchymal Stem Cells Resolve Airway Inflammation, Hyperreactivity, and Histopathology in a Mouse Model of Occupational Asthma

Martínez-González

Cruz

Moreno

et al. 2014

Stem Cells and Development

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“…Mice challenged with ovalbumin and then treated with anti-IL-33 antibody or sST2 showed negative regulation of ovalbumin-induced allergic airway inflammation (Lee et al, 2014); both treatments decreased Th2 cytokine levels in bronchoalveolar lavage fluid and decreased the count of eosinophils (Lee et al, 2014). One company has announced the production of a humanized anti-IL-33 antibody for clinical use (www.anaptysbio.com/ anti-il33).…”

Section: Treatment Possibilitiesmentioning

confidence: 99%

Targeting IL-33 in Autoimmunity and Inflammation

Theoharides

Petra

Taracanova

et al. 2015

J Pharmacol Exp Ther

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“…24 h before Lys-ASA). Goat anti-mouse IL-33 antibody (3.6 μg/mouse, R&D Systems, Minneapolis, MN) or recombinant mouse ST2-Fc fusion protein (5 μg/mouse, R&D Systems) (29) were given intraperitoneally at 24 h before Lys-ASA or LTE 4 challenge. The same amount of normal goat IgG (R&D Systems) and recombinant human IgG1 Fc (R&D Systems) were used as controls.…”

Section: Measurement Of Airway Resistancementioning

confidence: 99%

Aspirin Exacerbated Respiratory Disease Involves a Cysteinyl Leukotriene-Driven IL-33-Mediated Mast Cell Activation Pathway

Liu

Kanaoka

Barrett

et al. 2016

Journal of Allergy and Clinical Immunology

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Aspirin exacerbated respiratory disease (AERD), a severe eosinophilic inflammatory disorder of the airways, involves overproduction of cysteinyl leukotrienes (cysLTs), activation of airway mast cells (MCs), and bronchoconstriction in response to nonselective cyclooxygenase inhibitors that deplete homeostatic prostaglandin (PG)E 2 . The mechanistic basis for MC activation in this disorder is unknown. We now demonstrate that patients with AERD have markedly increased epithelial expression of the alarmin-like cytokine IL-33 in nasal polyps, as compared to polyps from aspirin tolerant (AT) controls. The murine model of AERD, generated by dust mite priming of mice lacking microsomal PGE 2 synthase (ptges −/− mice), shows a similar upregulation of IL-33 protein in the airway epithelium, along with marked eosinophilic bronchovascular inflammation. Deletion of LTC 4 synthase (LTC 4 S), the terminal enzyme needed to generate cysLTs, eliminates the increased IL-33 content of the ptges −/− lungs and sharply reduces pulmonary eosinophilia and basal secretion of MC products. Challenges of dust mite-primed ptges −/− mice with lysine aspirin (Lys-ASA) induce IL-33-dependent MC activation and bronchoconstriction. Thus, IL-33 is a component of a cysLT-driven innate type 2 immune response that drives pathogenic MC activation and contributes substantially to AERD pathogenesis.

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Blockade of IL-33/ST2 ameliorates airway inflammation in a murine model of allergic asthma

Abstract: These results suggest that anti-IL-33 as well as sST2 have therapeutic potential for allergic asthma through inhibition of Th2 cytokine production.

Cited by 113 publications

References 38 publications

Human Mesenchymal Stem Cells Resolve Airway Inflammation, Hyperreactivity, and Histopathology in a Mouse Model of Occupational Asthma

Human Mesenchymal Stem Cells Resolve Airway Inflammation, Hyperreactivity, and Histopathology in a Mouse Model of Occupational Asthma

Targeting IL-33 in Autoimmunity and Inflammation

Aspirin Exacerbated Respiratory Disease Involves a Cysteinyl Leukotriene-Driven IL-33-Mediated Mast Cell Activation Pathway

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