IL-21 and autoimmune disease--hypothesis and reality?

Previous data have indicated that IL-21 and/or IL-21R are crucial for the differentiation of naïve T cells into Th17 cells and also play a key role in the development of autoimmune disease. Given this, IL-21 and/or IL-21R are potential targets for therapy of such diseases; however, a study in this issue of the European Journal of Immunology, provides a new twist in the story as it is now shown that IL-21 and/or IL-21R play no role in Th17 development or autoimmune inflammatory disease. The reasons for these contradictory data are discussed in this Commentary.