An IL-1 cytokine member, IL-33, induces human basophil activation via its ST2 receptor.

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作者：

M Suzukawa，M Iikura，R Koketsu，H Nagase，C Tamura，A Komiya，S Nakae，K Matsushima，K Ohta，K Yamamoto

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摘要：

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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关键词：

Humans Basophils Cells, Cultured Receptors, Cell Surface Interleukins Basophil Degranulation Test Histamine Release Gene Expression Regulation Interleukin-1 Chemokine CCL11