A novel IL-1 family cytokine, IL-33, potently activates human eosinophils

Background Eosinophils are likely key cells involved in the pathogenesis of asthma and allergic diseases; however, the mechanisms that regulate eosinophil dynamics and functions in mucosal tissues are incompletely understood. IL-33, which is produced by mucosal cells, is a new member of the IL-1 cyt...

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Published in:	Journal of allergy and clinical immunology 2008-06, Vol.121 (6), p.1484-1490
Main Authors:	Cherry, W. Brett, MD, Yoon, Juhan, PhD, Bartemes, Kathleen R., BS, Iijima, Koji, PhD, Kita, Hirohito, MD
Format:	Article
Language:	eng
Subjects:	activation Allergy and Immunology Binding sites Biological and medical sciences Cell Degranulation - physiology Cytokines Cytokines - biosynthesis Enzyme-Linked Immunosorbent Assay Eosinophils Eosinophils - metabolism Flow Cytometry Fundamental and applied biological sciences. Psychology Fundamental immunology Gene expression Humans IL-33 inflammation Interleukin-1 - metabolism Interleukin-1 Receptor-Like 1 Protein Interleukin-33 Interleukins - metabolism Medical sciences Proteins Receptors, Cell Surface - metabolism Reverse Transcriptase Polymerase Chain Reaction Rodents Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis ST2 Studies
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Summary:	Background Eosinophils are likely key cells involved in the pathogenesis of asthma and allergic diseases; however, the mechanisms that regulate eosinophil dynamics and functions in mucosal tissues are incompletely understood. IL-33, which is produced by mucosal cells, is a new member of the IL-1 cytokine family. Mice injected with IL-33 display profound mucosal eosinophilia with associated pathologic changes. Although mast cells and TH 2 cells express the IL-33 receptor, ST2, the roles of IL-33 and ST2 in eosinophil biology are unknown. Objectives We investigated the effects of IL-33 on human eosinophils in vitro. Methods Eosinophils and neutrophils were isolated from blood of normal individuals and mildly atopic patients. Real-time RT-PCR and flow cytometry were used to detect ST2. Granulocyte responses to IL-33 were monitored by superoxide anion production and by degranulation; IL-5, IL-1β, and TNF-α served as controls. Eosinophil survival and cytokine production were assessed by flow cytometry and ELISA, respectively. Results ST2 mRNA and protein were detected on eosinophils. IL-33 induced eosinophil superoxide anion production and degranulation as potently as IL-5. IL-33 also increased eosinophil survival and induced production of IL-8. Anti-ST2 inhibited eosinophil responses to IL-33. Neutrophils did not express ST2, nor did they respond to IL-33. Conclusion IL-33 and its receptor, ST2, may play important roles in eosinophil-mediated inflammation; they may provide new therapeutic targets for controlling mucosal eosinophilic inflammation.
ISSN:	0091-6749 1097-6825