title: IL-21 receptor signaling is integral to the development of Th2 effector responses in vivo.
abstract: 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.
authors.affiliation: Institute of Integrative Biology, Molecular Biomedicine, Swiss Federal Institute of Technology (ETH) Zürich, Switzerland.
authors.forename: Anja
authors.initials: A
authors.lastname: Fröhlich
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Marsland
authors.forename: Ivo
authors.initials: I
authors.lastname: Sonderegger
authors.forename: Michael
authors.initials: M
authors.lastname: Kurrer
authors.forename: Martin R
authors.initials: MR
authors.lastname: Hodge
authors.forename: Nicola L
authors.initials: NL
authors.lastname: Harris
authors.forename: Manfred
authors.initials: M
authors.lastname: Kopf
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001982:Bronchial Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009205:Myocarditis / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009351:Nematospiroides dubius / Q000276:immunology; D009559:Nippostrongylus / Q000276:immunology; D053655:Receptors, Interleukin-21 / Q000172:deficiency / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism*
chemical_list: D053655:Receptors, Interleukin-21