IL-33 Exacerbates Eosinophil-Mediated Airway Inflammation

Stolarski, B., Kurowska-Stolarska, M. , Kewin, P., Xu, D. and Liew, F. Y. (2010) IL-33 Exacerbates Eosinophil-Mediated Airway Inflammation. Journal of Immunology, 185(6), pp. 3472-3480. (doi: 10.4049/jimmunol.1000730)

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IL-33 has emerged as an important mediator in the immunopathogenesis of allergy and asthma. However, the role of IL-33 in eosinophil-mediated inflammation has not been fully explored. In this article, we report that IL-33 directly stimulates eosinophil differentiation from CD117(+) progenitors in an IL-5-dependent manner. Although resting eosinophils expressed moderate levels of the IL-33R alpha-chain (ST2L), eosinophils that accumulated in the airways of mice with OVA-induced asthma expressed increased amounts of ST2L. In vitro, IL-33 and GM-CSF are potent inducers of ST2L expression on eosinophils, and IL-33 induced the production of IL-13, CCL17, and TGF-beta by eosinophils. In adoptive-transfer experiments, IL-33 exacerbated eosinophil-mediated airway inflammation by increasing the levels of eosinophils, macrophages, lymphocytes, IL-13, TGF-beta, CCL3, CCL17, and CCL24 in the lungs. IL-33 also enhanced the eosinophil-mediated differentiation of airway macrophages toward the alternatively activated macrophage phenotype in an IL-13-dependent manner. Taken together, this study demonstrates that the IL-33/ST2 signaling pathway activates airway eosinophils that exacerbate airway inflammation in an autocrine and paracrine manner.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Liew, Prof Foo and Xu, Dr Damo and Kurowska-Stolarska, Professor Mariola
Authors: Stolarski, B., Kurowska-Stolarska, M., Kewin, P., Xu, D., and Liew, F. Y.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Journal of Immunology
Publisher:American Association of Immunologists
ISSN (Online):1550-6606
Published Online:06 August 2010
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
486461The role of IL-35 in infection and inflammationFoo LiewMedical Research Council (MRC)G0801198Infection Immunity and Inflammation Medicine