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* Department of Allergy and Rheumatology, and
Department of Molecular Preventive Medicine, University of Tokyo Graduate School of Medicine,
Department of Respiratory Medicine, University of Teikyo School of Medicine,
Department of Respiratory Medicine, International Medical Center of Japan, and
¶ Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo, Japan
Basophils are thought to play pivotal roles in allergic inflammation through rapid release of chemical mediators in addition to sustained production of Th2 cytokines, including IL-4. A newly identified cytokine, IL-33, has been recognized as one of the key cytokines enhancing Th2-balanced immune regulation through its receptor, ST2. The present study was conducted to elucidate whether IL-33 acts directly on, and affects the functions of, human basophils. Real-time PCR analysis showed that basophils express transcripts for ST2. The expression levels were significantly higher compared with eosinophils and neutrophils, and treatment with IL-33 significantly up-regulated basophil ST2 mRNA expression. Expressions of IL-4 and IL-13 mRNA were also up-regulated by IL-33, and there was also enhanced secretion of IL-4 protein. IL-33 increased the surface levels of basophil CD11b expression and enhanced basophil adhesiveness. Although IL-33 failed to directly induce degranulation or attract basophils, it exerted priming effects on basophils. It enhanced degranulation in response to IgE-crosslinking stimulus and also enhanced basophil migration toward eotaxin without changing surface CCR3. Also, IL-33 synergistically enhanced IL-4 production and CD11b expression by IL-3-stimulated basophils. Neutralization using Ab specific for ST2 significantly diminished the enhancing effects of IL-33 on both basophil CD11b expression and migration toward eotaxin, indicating that IL-33 signals via ST2 expressed on basophils. This study revealed that IL-33 potently regulates migration and activation of human basophils. IL-33 may be a key cytokine in the pathogenesis of Th2-dominant inflammation by acting not only on lymphocytes but also on effector cells such as basophils.
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1 This work was supported by a grant from the Ministry of Labour, Health and Welfare of Japan, and a Long-range Research Initiative (LRI) grant from the Japan Chemical Industry Association.
2 Address correspondence and reprint requests to Dr. Maho Suzukawa, Department of Allergy and Rheumatology, University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. E-mail address: fueta-tky{at}umin.ac.jp
3 Abbreviations used in this paper: LT, leukotriene; HSA, human serum albumin; MESF, molecules of equivalent soluble fluorochrome unit; PI, propidium iodide.
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