IL-21 receptor signaling is integral to the development of Th2 effector responses in vivo

Blood. 2007 Mar 1;109(5):2023-31. doi: 10.1182/blood-2006-05-021600. Epub 2006 Oct 31.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / metabolism
  • Autoimmune Diseases / pathology
  • Bronchial Diseases / genetics
  • Bronchial Diseases / immunology
  • Bronchial Diseases / metabolism
  • Bronchial Diseases / pathology
  • Mice
  • Mice, Knockout
  • Myocarditis / genetics
  • Myocarditis / immunology
  • Myocarditis / metabolism
  • Myocarditis / pathology
  • Nematospiroides dubius / immunology
  • Nippostrongylus / immunology
  • Receptors, Interleukin-21 / deficiency
  • Receptors, Interleukin-21 / genetics
  • Receptors, Interleukin-21 / immunology*
  • Receptors, Interleukin-21 / metabolism
  • Signal Transduction / immunology*
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism*


  • Receptors, Interleukin-21