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The Journal of Immunology, 2007, 179, 2551 -2555
Copyright © 2007 by The American Association of Immunologists, Inc.
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IL-1 Receptor Accessory Protein and ST2 Comprise the IL-33 Receptor Complex

Alissa A. Chackerian, Elizabeth R. Oldham, Erin E. Murphy, Jochen Schmitz, Stefan Pflanz and Robert A. Kastelein1

Discovery Research, Schering-Plough Biopharma (formerly DNAX Research), Palo Alto, CA 94304

IL-33 (IL-1F11) is a recently described member of the IL-1 family of cytokines that stimulates the generation of cells, cytokines, and Igs characteristic of a type 2 immune response. IL-33 mediates signal transduction through ST2, a receptor expressed on Th2 and mast cells. In this study, we demonstrate that IL-33 and ST2 form a complex with IL-1R accessory protein (IL-1RAcP), a signaling receptor subunit that is also a member of the IL-1R complex. Additionally, IL-1RAcP is required for IL-33-induced in vivo effects, and IL-33-mediated signal transduction can be inhibited by dominant-negative IL-1RAcP. The implications of this shared usage of IL-1RAcP by IL-1({alpha} and beta) and IL-33 are discussed.

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 Address correspondence and reprint requests to Dr. Robert A. Kastelein, Discovery Research, Schering-Plough Biopharma (formerly DNAX Research), 901 California Avenue, Palo Alto, CA 94304. E-mail address: rob.kastelein{at}spcorp.com

2 Abbreviations used in this paper: IL-1RAcP, IL-1R accessory protein; dn, dominant negative; WT, wild type; TIR, Toll/IL-1R.




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