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.
