IL-21 receptor signaling is integral to the development of Th2 effector responses in vivo
Interleukin 21 (IL-21) is a member of the common gamma-chain family of cytokines, which influence a broad spectrum of immunologic responses. A number of studies have examined the function of IL-21, but 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, and Nippostrongylus brasiliensis and Heligmosomoides polygyrus antihelminth 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+/+/IL-21R-/- chimera mice revealed that IL-21R-signaling was central to Th2-cell survival or migration to peripheral tissues. Overall, our data show IL-21 plays a crucial role in supporting polarized Th2 responses in vivo, while appearing superfluous for Th1 and Th17 responses.
Keywords: Animals ; Autoimmune Diseases/genetics/immunology/metabolism/pathology ; Bronchial Diseases/genetics/immunology/metabolism/pathology ; Mice ; Mice, Knockout ; Myocarditis/genetics/immunology/metabolism/pathology ; Nematospiroides dubius/immunology ; Nippostrongylus/immunology ; Receptors, Interleukin-21/deficiency/genetics/*immunology/metabolism ; Signal Transduction/*immunology ; Th2 Cells/*immunology/*metabolism
Frohlich, Anja Marsland, Benjamin J Sonderegger, Ivo Kurrer, Michael Hodge, Martin R Harris, Nicola L Kopf, Manfred Research Support, Non-U.S. Gov't United States Blood Blood. 2007 Mar 1;109(5):2023-31. Epub 2006 Oct 31.
Record created on 2010-01-06, modified on 2016-08-08