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* Laboratory on Allergy, Centre Hospitalier de l’Université de Montréal Research Center, Notre-Dame Hospital, Montreal, Quebec, Canada and
Inflammation Research, Amgen, Seattle, WA 98101
IL-33, the natural ligand of the IL-1 receptor family member ST2L, is known to enhance experimental allergic-type inflammatory responses by costimulating the production of cytokines from activated Th2 lymphocytes. Although ST2L has long been known to be expressed by mast cells, its role in their biology has not been explored. In this study we report that IL-33 directly stimulates primary human mast cells (MCs) to produce several proinflammatory cytokines and chemokines and also exerts a permissive effect on the MCs response to thymic stromal lymphopoietin, a recently described potent MCs activator. IL-33 also acts both alone and in concert with thymic stromal lymphopoietin to accelerate the in vitro maturation of CD34+ MC precursors and induce the secretion of Th2 cytokines and Th2-attracting chemokines. Taken together, these results suggest that IL-33 may play an important role in mast cell-mediated inflammation and further emphasize the role of innate immunity in allergic diseases.
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 Amgen.
2 Address correspondence and reprint requests to Dr. Guy Delespesse, Centre Hospitalier de l’Université de Montréal Research Center, Notre-Dame Hospital, Laboratory on Allergy, 1560 Sherbrooke East Street, Pavillon Mailloux, M4211-K, Montreal, Quebec, Canada H2L-4M1. E-mail address: guy.delespesse{at}sympatico.ca
3 Abbreviations used in this paper: SST2, soluble ST2; LTC4, 5(S)-hydroxy-6(R)-S-glutathionyl-7,9-trans-11,14-cis-eicosatetraenoic acid; MC, mast cell; TSLP, thymic stromal lymphopoietin.
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