Immunity Article Interleukin-2 Signaling via STAT5

Recent work has identified a new subset of ef-fector T cells that produces interleukin (IL)-17 known as T helper 17 (Th17) cells, which is in-volved in the pathophysiology of inflammatory diseases and is thought to be developmentally related to regulatory T (Treg) cells. Because of its importance for Treg cells, we examined the role of IL-2 in Th17 generation and demonstrate that a previously unrecognized aspect of IL-2 function is to constrain IL-17 production. Genetic deletion or antibody blockade of IL-2 promoted differentiation of the Th17 cell sub-set. Whereas STAT3 appeared to be a key pos-itive regulator of RORgt and IL-17 expression, absence of IL-2 or disruption of its signaling by deletion of the transcription factor STAT5 re-sulted in enhanced Th17 cell development. We conclude that in addition to the promotion of activation-induced cell death of lymphocytes and the generation of Treg cells, inhibition of Th17 polarization appears to be an important function of IL-2