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.
Fröhlich
Anja
A
Institute of Integrative Biology, Molecular Biomedicine, Swiss Federal Institute of Technology (ETH) Zürich, Switzerland.
Marsland
Benjamin J
BJ
Sonderegger
Ivo
I
Kurrer
Michael
M
Hodge
Martin R
MR
Harris
Nicola L
NL
Kopf
Manfred
M
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*
D053655:Receptors, Interleukin-21