IL-33 Amplifies the Polarization of Alternatively Activated Macrophages That Contribute to Airway Inflammation

Kurowska-Stolarska, M. et al. (2009) IL-33 Amplifies the Polarization of Alternatively Activated Macrophages That Contribute to Airway Inflammation. Journal of Immunology, 183(10), pp. 6469-6477. (doi: 10.4049/jimmunol.0901575) (PMID:19841166)

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Alternatively activated macrophages (AAM) play a crucial role in type 2 immunity. Mice deficient in ST2, a receptor for the latest member of the IL-1 family, IL-33, have impaired type 2 immune responses. We therefore reasoned that IL-33/ST2 signaling may be involved in the differentiation and activation of AAM during airway inflammation. We report here that IL-33 changed the quiescent phenotype of alveolar macrophages toward an AAM phenotype that expressed mannose receptor, IL-4Rα, and produced high levels of CCL24 and CCL17 in an IL-13-dependent manner during IL-33-induced airway inflammation. Neutralization of AAM-derived CCL24 led to an amelioration of IL-33-induced eosinophilia in the lungs. Moreover, depletion of alveolar macrophages reduced IL-33-induced airway inflammation. Additionally, the attenuated OVA-induced airway inflammation in ST2−/− mice was associated with a decrease in AAM differentiation. In vitro, IL-33 amplified IL-13-induced polarization of alveolar- and bone marrow-derived macrophage toward an AAM phenotype by increasing the expression of arginase I, Ym1, as well as the production of CCL24 and CCL17. IL-13/IL-4Rα signaling was crucial for IL-33-driven AAM amplification by inducing the expression of ST2L. Finally, we showed that IL-33 was more abundantly expressed in the lung epithelial cells of asthma patients than those from healthy controls, suggesting that IL-33 may be involved in lung macrophage activation in clinical asthma. Taken together, we demonstrate here that IL-33/ST2 plays a significant role in the amplification of AAM polarization and chemokine production which contribute to innate and Ag-induced airway inflammation.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Liew, Prof Foo and McInnes, Professor Iain and Mirchandani, Dr Ananda and Xu, Dr Damo and Murphy, Dr Grace and Pitman, Dr Nick and Kurowska-Stolarska, Professor Mariola and McSharry, Dr Charles and Shepherd, Professor Malcolm
Authors: Kurowska-Stolarska, M., Stolarski, B., Kewin, P., Murphy, G., Corrigan, C. J., Ying, S., Pitman, N., Mirchandani, A., Rana, B., van Rooijen, N., Shepherd, M., McSharry, C., McInnes, I. B., Xu, D., and Liew, F. Y.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Clinical Specialities
Journal Name:Journal of Immunology
Journal Abbr.:J. Immunol.
Publisher:American Association of Immunologists
ISSN (Online):1550-6606
Published Online:15 November 2009

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
378571The role of a novel cytokine (EB13-IL12p35) in asthmaNick PitmanMedical Research Council (MRC)G84/6704Institute of Infection Immunity and Inflammation
522591The role of nitric oxide-induced regulatory T cells in inflammationFoo LiewMedical Research Council (MRC)G0902003Infection Immunity and Inflammation Medicine
445191The role of the 1L-33 in the innate and adaptive immune responses in asthmaGrace MurphyMedical Research Council (MRC)G0601422III -IMMUNOLOGY