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Blood, 1 March 2007, Vol. 109, No. 5, pp. 2023-2031. Prepublished online as a Blood First Edition Paper on October 31, 2006; DOI 10.1182/blood-2006-05-021600. This Article Full Text (PDF) All Versions of this Article: blood-2006-05-021600v1 109/5/2023    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Frohlich, A. Articles by Kopf, M. Search for Related Content PubMed PubMed Citation Articles by Frohlich, A. Articles by Kopf, M. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 9, 2006 Accepted October 10, 2006 IL-21 receptor signaling is integral to the development of Th2 effector responses in vivo Anja Frohlich, Benjamin J Marsland, Ivo Sonderegger, Michael Kurrer, Martin R Hodge, Nicola L Harris, and Manfred Kopf* Institute of Integrative Biology, Molecular Biomedicine, ETH Zurich, Switzerland Dept of Pathology, University Zurich, Switzerland Inflammation Division, Millenium Pharmaceuticals, Inc., Cambridge, MA, United States Institute of Integrative Biology, Environmental Biomedicine, ETH Zurich, Switzerland * Corresponding author; email: manfred.kopf{at}ethz.ch. Interleukin 21 (IL-21) is a member of the common -chain family of cytokines, which influence a broad spectrum of immunological responses. A number of studies have examined the function of IL-21; however, its specific role in Th1/ Th2 cell differentiation and related effector responses remains to be clarified. Thus, we generated IL-21R-deficient mice and have investigated the role of IL-21R signaling using a series of in vivo experimentally induced disease models. We first addressed the role of IL-21R signaling in Th2 immune responses by examining allergic airway inflammation, Nippostrongylus brasiliensis and Heligomosomoides polygyrus anti-helminth responses. In each of these systems, IL-21R signaling played a clear role in the development of Th2 responses. Comparatively, IL-21R signaling was not required for the containment of Leishmania major infection, or the development of experimental autoimmune myocarditis, indicative of competent Th1 and Th17 responses, respectively. Adoptive transfer of T cells and analysis of IL-21R+/+:-/- chimera mice revealed that IL-21R-signaling was central to Th2 cell survival or migration to peripheral tissues. Overall, our data shows IL-21 plays a crucial role in supporting polarized Th2 responses in vivo, whilst appearing superfluous for Th1 and Th17 responses. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. R. Ramalingam, J. T. Pesce, M. M. Mentink-Kane, S. Madala, A. W. Cheever, M. R. Comeau, S. F. Ziegler, and T. A. Wynn Regulation of Helminth-Induced Th2 Responses by Thymic Stromal Lymphopoietin J. Immunol., May 15, 2009; 182(10): 6452 - 6459. [Abstract] [Full Text] [PDF] A. G. Zaretsky, J. J. Taylor, I. L. King, F. A. Marshall, M. Mohrs, and E. J. Pearce T follicular helper cells differentiate from Th2 cells in response to helminth antigens J. Exp. Med., May 11, 2009; 206(5): 991 - 999. [Abstract] [Full Text] [PDF] F. Eddahri, S. 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Coquet, S. Chakravarti, M. J. Smyth, and D. I. Godfrey Cutting Edge: IL-21 Is Not Essential for Th17 Differentiation or Experimental Autoimmune Encephalomyelitis J. Immunol., June 1, 2008; 180(11): 7097 - 7101. [Abstract] [Full Text] [PDF] L. E. Clough, C. J. Wang, E. M. Schmidt, G. Booth, T. Z. Hou, G. A. Ryan, and L. S. K. Walker Release from Regulatory T Cell-Mediated Suppression during the Onset of Tissue-Specific Autoimmunity Is Associated with Elevated IL-21 J. Immunol., April 15, 2008; 180(8): 5393 - 5401. [Abstract] [Full Text] [PDF] I. D. Davis, K. Skak, M. J. Smyth, P. E.G. Kristjansen, D. M. Miller, and P. V. Sivakumar Interleukin-21 Signaling: Functions in Cancer and Autoimmunity Clin. Cancer Res., December 1, 2007; 13(23): 6926 - 6932. [Abstract] [Full Text] [PDF] L. Wei, A. Laurence, K. M. Elias, and J. J. O'Shea IL-21 Is Produced by Th17 Cells and Drives IL-17 Production in a STAT3-dependent Manner J. Biol. Chem., November 30, 2007; 282(48): 34605 - 34610. 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