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This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: jimmunol.0900328v1 183/6/3591    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Schneider, E. Articles by Dy, M. PubMed PubMed Citation Articles by Schneider, E. Articles by Dy, M.

IL-33 Activates Unprimed Murine Basophils Directly In Vitro and Induces Their In Vivo Expansion Indirectly by Promoting Hematopoietic Growth Factor Production¹

Elke Schneider^2,*, Anne-France Petit-Bertron^*, Rachel Bricard^*, Mélanie Levasseur^*, Abdelrauf Ramadan^*, Jean-Philippe Girard, André Herbelin^* and Michel Dy^*

^* Université Paris Descartes, Faculté de Médecine-Centre National de la Recherche Scientifique Unité Mixte de Recherche 8147, Paris, France; and IPBS-Centre National de la Recherche-Unité Mixte de Recherche 5089, University of Toulouse, Toulouse, France

IL-33, a new member of the IL-1 family, has been described as an important inducer of Th2 cytokines and mediator of inflammatory responses. In this study, we demonstrate that murine basophils sorted directly from the bone marrow, without prior exposure to IL-3 or FcR cross-linking, respond to IL-33 alone by producing substantial amounts of histamine, IL-4, and IL-6. These cells express ST2 constitutively and generate a cytokine profile that differs from their IL-3-induced counterpart by a preferential production of IL-6. In vivo, IL-33 promotes basophil expansion in the bone marrow (BM) through an indirect mechanism of action depending on signaling through the β_c chain shared by receptors for IL-3, GM-CSF, and IL-5. IL-3 can still signal through its specific β_IL-3 chain in these mutant mice, which implies that it is not the unique growth-promoting mediator in this setup, but requires IL-5 and/or GMCSF. Our results support a major role of the latter growth factor, which is readily generated by total BM cells as well as sorted basophils in response to IL-33 along with low amounts of IL-3. Furthermore, GM-CSF amplifies IL-3-induced differentiation of basophils from BM cells, whereas IL-5 that is also generated in vivo, affects neither their functions nor their growth in vitro or in vivo. In conclusion, our data provide the first evidence that IL-33 not only activates unprimed basophils directly, but also promotes their expansion in vivo through induction of GM-CSF and IL-3.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by a grant from the Agence Nationale pour la Recherche (Immunoregulatory functions of Histamine through Organic Cation Transporter 3 (OCT3) and H4 receptors (H4R), new targets for anti-allergic treatment).

² Address correspondence and reprint requests to Dr. Elke Schneider, Centre National de la Recherche Unité 8147, Hôpital Necker, 161 rue de Sèvres, 75783 Paris, Cedex, France. E-mail address: schneider{at}necker.fr

³ Abbreviations used in this paper: BM, bone marrow; BMDB, BM-derived basophil; mr, murine recombinant.

⁴ The online version of this article contains supplemental material.