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Published online before print September 19, 2007

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0407200

Received for publication April 2, 2007.
Revised August 20, 2007.
Accepted for publication August 29, 2007.

Article

IL-33 induces IL-13 production by mouse mast cells independently of IgE-FcRI signals

Lien H. Ho ^*, Tatsukuni Ohno , Keisuke Oboki , Naoki Kajiwara , Hajime Suto ^*, Motoyasu Iikura ^*||, Yoshimichi Okayama , Shizuo Akira ^¶, Hirohisa Saito , Stephen J. Galli ^*@, and Susumu Nakae ^*@

*Department of Pathology, Stanford University School of Medicine, Stanford, California, USA; Department of Allergy and Immunology, National Research Institute for Child Health & Development, Tokyo, Japan; Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Center, Nihon University Graduate School of Medical Sciences, Tokyo, Japan; Atopy Research Center, Juntendo University, Tokyo, Japan; ^||Department of Respiratory Medicine, National Disaster Medical Center of Japan, Tokyo, Japan; and ^¶Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan

^@ To whom correspondence should be addressed. E-mail: sgalli{at}stanford.edu.

	Abstract

The IL-1-related molecules, IL-1 and IL-18, can promote Th2 cytokine production by IgE/antigen-FcRI-stimulated mouse mast cells. Another IL-1-related molecule, IL-33, was identified recently as a ligand for T1/ST2. Although mouse mast cells constitutively express ST2, the effects of IL-33 on mast cell function are poorly understood. We found that IL-33, but not IL-1 or IL-18, induced IL-13 and IL-6 production by mouse bone marrow-derived, cultured mast cells (BMCMCs) independently of IgE. In BMCMCs incubated with the potently cytokinergic SPE-7 IgE without specific antigen, IL-33, IL-1, and IL-18 each promoted IL-13 and IL-6 production, but the effects of IL-33 were more potent than those of IL-1 or IL-18. IL-33 promoted cytokine production via a MyD88-dependent but Toll/IL-1R domain-containing adaptor-inducing IFN--independent pathway. By contrast, IL-33 neither induced nor enhanced mast cell degranulation. At 200 ng/ml, IL-33 prolonged mast cell survival in the absence of IgE and impaired survival in the presence of SPE-7 IgE, whereas at 100 ng/ml, IL-33 had no effect on mast cell survival in the absence of IgE and reduced mast cell survival in the presence of IgE. These observations suggest potential roles for IL-33 in mast cell- and Th2 cytokine-associated immune responses and disorders.

Key Words: cytokines • Fc receptors • mast cells/basophils • allergy

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